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Cell therapy using ex vivo reprogrammed macrophages enhances antitumor immune responses in melanoma

Macrophage-based cell therapies have shown modest success in clinical trials, which can be attributed to their phenotypic plasticity, where transplanted macrophages get reprogrammed towards a pro-tumor phenoty...

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In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma

For angioimmunoblastic T cell lymphoma (AITL), a rare cancer, no specific treatments are available and survival outcome is poor. We previously developed a murine model for AITL that mimics closely human diseas...

Recruitment of USP10 by GCS1 to deubiquitinate GRP78 promotes the progression of colorectal cancer via alleviating endoplasmic reticulum stress

Long-term accumulation of misfolded proteins leads to endoplasmic reticulum (ER) stress in colorectal cancer (CRC). However, the precise pathways controlling the decision between survival and apoptosis in CRC ...

STUB1-mediated K63-linked ubiquitination of UHRF1 promotes the progression of cholangiocarcinoma by maintaining DNA hypermethylation of PLA2G2A

Cholangiocarcinoma (CCA) is a highly malignant tumor characterized by a lack of effective targeted therapeutic strategies. The protein UHRF1 plays a pivotal role in the preservation of DNA methylation and work...

Challenges in validation of combination treatment strategies for CRC using patient-derived organoids

Patient-derived organoids (PDOs) established from tissues from various tumor types gave the foundation of ex vivo models to screen and/or validate the activity of many cancer drug candidates. Due to their phen...

Tumor-associated neutrophils upregulate Nectin2 expression, creating the immunosuppressive microenvironment in pancreatic ductal adenocarcinoma

Tumor-associated neutrophils (TANs) constitute an abundant component among tumor-infiltrating immune cells and have recently emerged as a critical player in pancreatic ductal adenocarcinoma (PDAC) progression....

Correction: Anti-tumor effects of ONC201 in combination with VEGF-inhibitors significantly impacts colorectal cancer growth and survival in vivo through complementary non-overlapping mechanisms

The original article was published in Journal of Experimental & Clinical Cancer Research 2018 37 :11

Correction: Novel engineered IL-2 Nemvaleukin alfa combined with PD1 checkpoint blockade enhances the systemic anti-tumor responses of radiation therapy

The original article was published in Journal of Experimental & Clinical Cancer Research 2024 43 :251

Membrane RRM2-positive cells represent a malignant population with cancer stem cell features in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is one of the most lethal malignancies and highly heterogeneous. We thus aimed to identify and characterize iCCA cell subpopulations with severe malignant features.

Why make it if you can take it: review on extracellular cholesterol uptake and its importance in breast and ovarian cancers

Cholesterol homeostasis is essential for healthy mammalian cells and dysregulation of cholesterol metabolism contributes to the pathogenesis of various diseases including cancer. Cancer cells are dependent on ...

HSF1 is a prognostic determinant and therapeutic target in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a lethal primary liver tumor characterized by clinical aggressiveness, poor prognosis, and scarce therapeutic possibilities. Therefore, new treatments are urgently nee...

The dual role of POSTN in maintaining glioblastoma stem cells and the immunosuppressive phenotype of microglia in glioblastoma

Glioblastoma (GBM) is an immunosuppressive, universally lethal cancer driven by glioblastoma stem cells (GSCs). The interplay between GSCs and immunosuppressive microglia plays crucial roles in promoting the m...

Novel engineered IL-2 Nemvaleukin alfa combined with PD1 checkpoint blockade enhances the systemic anti-tumor responses of radiation therapy

Combining interleukin-2 (IL-2) with radiotherapy (RT) and immune checkpoint blockade (ICB) has emerged as a promising approach to address ICB resistance. However, conventional IL-2 cytokine therapy faces const...

The Correction to this article has been published in Journal of Experimental & Clinical Cancer Research 2024 43 :256

Multibiomarker panels in liquid biopsy for early detection of pancreatic cancer – a comprehensive review

Pancreatic ductal adenocarcinoma (PDAC) is frequently detected in late stages, which leads to limited therapeutic options and a dismal overall survival rate. To date, no robust method for the detection of earl...

USP36 promotes tumorigenesis and tamoxifen resistance in breast cancer by deubiquitinating and stabilizing ERα

Breast cancer is the most prevalent cancer in women globally. Over-activated estrogen receptor (ER) α signaling is considered the main factor in luminal breast cancers, which can be effectively managed with se...

Synthetic lethality of combined ULK1 defection and p53 restoration induce pyroptosis by directly upregulating GSDME transcription and cleavage activation through ROS/NLRP3 signaling

High expression of ubiquitin ligase MDM2 is a primary cause of p53 inactivation in many tumors, making it a promising therapeutic target. However, MDM2 inhibitors have failed in clinical trials due to p53-indu...

Co-delivery of camptothecin and MiR-145 by lipid nanoparticles for MRI-visible targeted therapy of hepatocellular carcinoma

Camptothecin (CPT) is one of the frequently used small chemotherapy drugs for treating hepatocellular carcinoma (HCC), but its clinical application is limited due to severe toxicities and acquired resistance. ...

Retraction Note: HOXD9 promotes epithelial–mesenchymal transition and cancer metastasis by ZEB1 regulation in hepatocellular carcinoma

Cct3/actn4/tfrc axis protects hepatocellular carcinoma cells from ferroptosis by inhibiting iron endocytosis.

Sorafenib is widely used in treating advanced hepatocellular carcinoma (HCC). However, its effectiveness in prolonging patient survival is limited by the development of drug resistance. To systematically inves...

Correction: TFEB controls sensitivity to chemotherapy and immuno-killing in non-small cell lung cancer

The original article was published in Journal of Experimental & Clinical Cancer Research 2024 43 :219

Correction: Bispecifc aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies

The original article was published in Journal of Experimental & Clinical Cancer Research 2024 43 :92

Molecular understanding and clinical aspects of tumor-associated macrophages in the immunotherapy of renal cell carcinoma

Renal cell carcinoma (RCC) is one of the most common tumors that afflicts the urinary system, accounting for 90–95% of kidney cancer cases. Although its incidence has increased over the past decades, its patho...

Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study

Factors to accurately stratify patients with early-stage non-small cell lung cancer (NSCLC) in different prognostic groups are still needed. This study aims to investigate 1) the prognostic potential of circul...

Identification of circulating tumor cells captured by the FDA-cleared Parsortix ® PC1 system from the peripheral blood of metastatic breast cancer patients using immunofluorescence and cytopathological evaluations

Circulating Tumor Cells (CTCs) may serve as a non-invasive source of tumor material to investigate an individual’s disease in real-time. The Parsortix ® PC1 System, the first FDA-cleared medical device for the cap...

Connecting the dots: investigating the link between environmental, genetic, and epigenetic influences in metabolomic alterations in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) accounts for around 90% of all oral cancers and is the eighth most common cancer worldwide. Despite progress in managing OSCC, the overall prognosis remains poor, with a sur...

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy

Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigate...

Two-polarized roles of transcription factor FOSB in lung cancer progression and prognosis: dependent on p53 status

Activator protein-1 (AP-1) represents a transcription factor family that has garnered growing attention for its extensive involvement in tumor biology. However, the roles of the AP-1 family in the evolution of...

The DNA repair pathway as a therapeutic target to synergize with trastuzumab deruxtecan in HER2-targeted antibody–drug conjugate–resistant HER2-overexpressing breast cancer

Anti-HER2 therapies, including the HER2 antibody–drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have led to improved survival outcomes in patients with HER2-overexpres...

The deubiquitinase USP15 drives malignant progression of gastric cancer through glucose metabolism remodeling

Ubiquitin-specific protease 15 (USP15) exhibits amplifications in various tumors, including gastric cancer (GC), yet its biological function and mechanisms in GC progression remain elusive.

Repurposed AT9283 triggers anti-tumoral effects by targeting MKK3 oncogenic functions in Colorectal Cancer

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide, with a survival rate near to 10% when diagnosed at an advanced stage. Hence, the...

Areca nut-induced metabolic reprogramming and M2 differentiation promote OPMD malignant transformation

Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant trans...

Targeting treatment resistance: unveiling the potential of RNA methylation regulators and TG-101,209 in pan-cancer neoadjuvant therapy

Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk o...

SelK promotes glioblastoma cell proliferation by inhibiting β-TrCP1 mediated ubiquitin-dependent degradation of CDK4

Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the b...

tsRNA-GlyGCC promotes colorectal cancer progression and 5-FU resistance by regulating SPIB

tRNA-derived small RNAs (tsRNAs) are newly discovered non-coding RNA, which are generated from tRNAs and are reported to participate in several biological processes in diseases, especially cancer; however, the...

Correction: Different p53 genotypes regulating different phosphorylation sites and subcellular location of CDC25C associated with the formation of polyploid giant cancer cells

The original article was published in Journal of Experimental & Clinical Cancer Research 2020 39 :83

Correction: Deliberation concerning the role of M1-type macrophage subset in oral carcinogenesis

The original article was published in Journal of Experimental & Clinical Cancer Research 2024 43 :220

Palmitoyltransferase ZDHHC6 promotes colon tumorigenesis by targeting PPARγ-driven lipid biosynthesis via regulating lipidome metabolic reprogramming

The failure of proper recognition of the intricate nature of pathophysiology in colorectal cancer (CRC) has a substantial effect on the progress of developing novel medications and targeted therapy approaches....

Circulating interleukin-8 and osteopontin are promising biomarkers of clinical outcomes in advanced melanoma patients treated with targeted therapy

Circulating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseli...

LINC00460/miR-186-3p/MYC feedback loop facilitates colorectal cancer immune escape by enhancing CD47 and PD-L1 expressions

Long non-coding RNAs (LncRNAs) have been implicated as critical regulators of cancer tumorigenesis and progression. However, their functions and molecular mechanisms in colorectal cancer (CRC) still remain to ...

Galectin-3 induces pathogenic immunosuppressive macrophages through interaction with TREM2 in lung cancer

High infiltration of tumor-associated macrophages (TAMs) is associated with tumor promotion and immunosuppression. The triggering receptor expressed on myeloid cells 2 (TREM2) is emerged as a key immunosuppres...

Synergistic intravesical instillation for bladder cancer: CRISPR-Cas13a and fenbendazole combination therapy

CRISPR-Cas13a is renowned for its precise and potent RNA editing capabilities in cancer therapy. While various material systems have demonstrated efficacy in supporting CRISPR-Cas13a to execute cellular functi...

Autophagy-mediated ID1 turnover dictates chemo-resistant fate in ovarian cancer stem cells

The mechanisms enabling dynamic shifts between drug-resistant and drug-sensitive states in cancer cells are still underexplored. This study investigated the role of targeted autophagic protein degradation in r...

Correction: The number of polyploid giant cancer cells and epithelial-mesenchymal transitionrelated proteins are associated with invasion and metastasis in human breast cancer

The original article was published in Journal of Experimental & Clinical Cancer Research 2015 34 :158

Deliberation concerning the role of M1-type macrophage subset in oral carcinogenesis

Over the last decade, accumulating evidence has suggested that tumor-associated macrophages (TAMs) play a significant role in the tumor development. This commentary wishes to highlight the findings by You, et ...

The Correction to this article has been published in Journal of Experimental & Clinical Cancer Research 2024 43 :228

TFEB controls sensitivity to chemotherapy and immuno-killing in non-small cell lung cancer

In non-small cell lung cancer (NSCLC) the efficacy of chemo-immunotherapy is affected by the high expression of drug efflux transporters as ABCC1 and by the low expression of ABCA1, mediating the isopentenyl p...

The Correction to this article has been published in Journal of Experimental & Clinical Cancer Research 2024 43 :244

Progesterone boosts abiraterone-driven target and NK cell therapies against glioblastoma

Glioblastoma (GBM) poses a significant challenge in oncology, with median survival times barely extending beyond a year due to resistance to standard therapies like temozolomide (TMZ). This study introduces a ...

Regulatory role of lncH19 in RAC1 alternative splicing: implication for RAC1B expression in colorectal cancer

Aberrant alternative splicing events play a critical role in cancer biology, contributing to tumor invasion, metastasis, epithelial-mesenchymal transition, and drug resistance. Recent studies have shown that a...

Examining the evidence for mutual modulation between m6A modification and circular RNAs: current knowledge and future prospects

The resistance of cancer cells to treatment significantly impedes the success of therapy, leading to the recurrence of various types of cancers. Understanding the specific mechanisms of therapy resistance may ...

The landscape of circulating tumor HPV DNA and TTMV-HPVDNA for surveillance of HPV-oropharyngeal carcinoma: systematic review and meta-analysis

Human papilloma virus (HPV) related cancers of the oropharynx are rapidly increasing in incidence and may soon represent the majority of all head and neck cancers. Improved monitoring and surveillance methods ...

Tumor-derived GLI1 promotes remodeling of the immune tumor microenvironment in melanoma

Melanoma progression is based on a close interaction between cancer cells and immune cells in the tumor microenvironment (TME). Thus, a better understanding of the mechanisms controlling TME dynamics and compo...

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An audit of metastatic tumors to the liver highlighting the spectrum of differential diagnosis: A retrospective study from a tertiary cancer center in North India

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Collection  10 March 2022

Top 100 in Cancer

This collection highlights our most downloaded* cancer papers published in 2021. Featuring authors from aroud the world, these papers showcase valuable research from an international community.

*Data obtained from SN Insights which is based on Digital Science's Dimensions.

Radiotherapy for brain metastasis and long-term survival

• Kawngwoo Park
• Gi Hwan Bae
• Jaehun Jung

The Angelina Jolie effect: Contralateral risk-reducing mastectomy trends in patients at increased risk of breast cancer

• Narendra Nath Basu
• James Hodson
• D. Gareth Evans

Deep learning classification of lung cancer histology using CT images

• Tafadzwa L. Chaunzwa
• Ahmed Hosny
• Hugo J. W. L. Aerts

Pancancer survival analysis of cancer hallmark genes

• Gyöngyi Munkácsy
• Balázs Győrffy

Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer

• Dina M. El-Kersh
• Shahira M. Ezzat
• Mohey M. Elmazar

Arsenic exposure in Indo Gangetic plains of Bihar causing increased cancer risk

• Mohammad Ali
• Ashok Kumar Ghosh

CIBERSORT analysis of TCGA and METABRIC identifies subgroups with better outcomes in triple negative breast cancer

• Kelly E. Craven
• Yesim Gökmen-Polar
• Sunil S. Badve

The incidence and clinical analysis of non-melanoma skin cancer

• Magdalena Ciążyńska
• Grażyna Kamińska-Winciorek
• Aleksandra Lesiak

Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands

• Christine M. Cramer-van der Welle
• Marjon V. Verschueren
• The Santeon NSCLC Study Group

Anti-tumour activity of deer growing antlers and its potential applications in the treatment of malignant gliomas

• Louis Chonco
• Tomás Landete-Castillejos
• Tomás Segura

Risk of cancer development in patients with keloids

• Hung-Pin Tu
• Chih-Hung Lee

Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases

• Bicky Thapa
• Manmeet S. Ahluwalia

Prediction of survival in patients with advanced, refractory colorectal cancer in treatment with trifluridine/tipiracil: real-world vs clinical trial data

• Ana Fernández Montes
• Alberto Carmona-Bayonas
• Teresa Garcia García

Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

• Shao-Yuan Chen
• Koichi Tsuneyama
• Shih-Ming Huang

Histopathological analysis of mucinous breast cancer subtypes and comparison with invasive carcinoma of no special type

• Michał Piotr Budzik
• Marta Magdalena Fudalej
• Anna Maria Badowska-Kozakiewicz

Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT

• Guiyang Hao
• Tara Mastren
• Xiankai Sun

Associations between the gut microbiome and fatigue in cancer patients

• Joud Hajjar
• Tito Mendoza

cGAS–STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells

• Manuel Adrian Suter
• Nikki Y. Tan
• Y. L. Zhang

Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray

• Yuya Higashi
• Kotaro Matsumoto
• Fuyuhiko Tamanoi

COVID-19 engages clinical markers for the management of cancer and cancer-relevant regulators of cell proliferation, death, migration, and immune response

• Serhiy Souchelnytskyi
• Andriy Nera
• Nazariy Souchelnytskyi

High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

• Haowen Xiao

Sensitivity, specificity, and accuracy of a liquid biopsy approach utilizing molecular amplification pools

• Jessica Garcia
• Nick Kamps-Hughes
• Cristian Ionescu-Zanetti

A survival analysis of surgically treated incidental low-grade glioma patients

• Lingcheng Zeng

Integrated multi-omics analysis of ovarian cancer using variational autoencoders

• Muta Tah Hira
• M. A. Razzaque
• Mosharraf Sarker

Cell-free DNA concentration and fragment size as a biomarker for prostate cancer

• Emmalyn Chen
• Clinton L. Cario
• John S. Witte

Real-world outcomes of first-line pembrolizumab plus pemetrexed-carboplatin for metastatic nonsquamous NSCLC at US oncology practices

• Vamsidhar Velcheti
• Thomas Burke

Graphene oxide loaded with tumor-targeted peptide and anti-cancer drugs for cancer target therapy

Comprehensive analysis of metastatic gastric cancer tumour cells using single-cell RNA-seq

• Yingyi Zhang
• Xianbao Zhan

Ex vivo culture of intact human patient derived pancreatic tumour tissue

• John Kokkinos
• George Sharbeen
• Phoebe A. Phillips

A phase 2a clinical study on the safety and efficacy of individualized dosed mebendazole in patients with advanced gastrointestinal cancer

• S. Mansoori

Palliative radiation therapy for symptomatic advance breast cancer

• Galia Jacobson
• Orit Kaidar-Person
• Merav Akiva Ben-David

Deep learning identifies morphological features in breast cancer predictive of cancer ERBB2 status and trastuzumab treatment efficacy

• Dmitrii Bychkov
• Nina Linder
• Johan Lundin

A prostate-specific membrane antigen (PSMA)-targeted prodrug with a favorable in vivo toxicity profile

• Srikanth Boinapally
• Hye-Hyun Ahn
• Martin G. Pomper

Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer

• Franceska Dedeurwaerdere
• Kathleen BM Claes
• Geert Martens

Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications

• Fengqin Shi

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20 + B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis

• Chengxin Luo

Morphofunctional analysis of human pancreatic cancer cell lines in 2- and 3-dimensional cultures

• Fuuka Minami
• Norihiko Sasaki
• Toshiyuki Ishiwata

Potentiality of multiple modalities for single-cell analyses to evaluate the tumor microenvironment in clinical specimens

• Yukie Kashima
• Yosuke Togashi
• Toshihiko Doi

Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening

• Aragaw Gebeyehu
• Sunil Kumar Surapaneni
• Mandip Singh

PTEN loss promotes oncogenic function of STMN1 via PI3K/AKT pathway in lung cancer

• Guangsu Xun

Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease

• Stephanie L. Rellick
• Gangqing Hu
• Laura F. Gibson

Effect of SSRI exposure on the proliferation rate and glucose uptake in breast and ovary cancer cell lines

• Britta Stapel
• Catharina Melzer

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

• Erik Brodin
• Paul Macklin

Pembrolizumab in vaginal and vulvar squamous cell carcinoma: a case series from a phase II basket trial

• Jeffrey A. How
• Amir A. Jazaeri

Relationship of breast volume, obesity and central obesity with different prognostic factors of breast cancer

• Daniel María Lubián López
• Carmen Aisha Butrón Hinojo
• Ernesto González Mesa

Meta-analysis of host transcriptional responses to SARS-CoV-2 infection reveals their manifestation in human tumors

• Fengju Chen
• Yiqun Zhang
• Chad J. Creighton

Selection and characterisation of Affimers specific for CEA recognition

• Shazana Hilda Shamsuddin
• David G. Jayne
• Paul A. Millner

Epidemiology and prognosis in young lung cancer patients aged under 45 years old in northern China

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer

• M. Ruiz-Borrego

Classification of paediatric brain tumours by diffusion weighted imaging and machine learning

• Niloufar Zarinabad
• Andrew Peet

Metagenomic analysis of formalin-fixed paraffin-embedded tumor and normal mucosa reveals differences in the microbiome of colorectal cancer patients

• Gabriela Debesa-Tur
• Vicente Pérez-Brocal
• Andrés Moya

A novel proteomics approach to epigenetic profiling of circulating nucleosomes

• Priscilla Van den Ackerveken
• Alison Lobbens
• Marielle Herzog

A review and comparison of breast tumor cell nuclei segmentation performances using deep convolutional neural networks

• Andrew Lagree
• Majidreza Mohebpour
• William T. Tran

Comparative analysis of machine learning approaches to classify tumor mutation burden in lung adenocarcinoma using histopathology images

• Apaar Sadhwani
• Huang-Wei Chang
• Peter Cimermancic

Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer

• Shiro Fujita
• Katsuhiro Masago

Anticancer potential of rhizome extract and a labdane diterpenoid from Curcuma mutabilis plant endemic to Western Ghats of India

• T. Lakshmipriya
• P. R. Manish Kumar

Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer

• Yoshihisa Shimada
• Jun Matsubayashi
• Norihiko Ikeda

Transcript levels of keratin 1/5/6/14/15/16/17 as potential prognostic indicators in melanoma patients

• Guo-Liang Shen

Enhancing the landscape of colorectal cancer using targeted deep sequencing

• Chul Seung Lee
• In Hye Song
• Sung Hak Lee

PGMD/curcumin nanoparticles for the treatment of breast cancer

• Mankamna Kumari
• Nikita Sharma
• Surendra Nimesh

GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

• Fahimeh Afzaljavan
• Ayeh Sadat Sadr
• Alireza Pasdar

Explainable drug sensitivity prediction through cancer pathway enrichment

• Yi-Ching Tang
• Assaf Gottlieb

A novel biosensor for the ultrasensitive detection of the lncRNA biomarker MALAT1 in non-small cell lung cancer

• Dongming Wu

Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

• Siyuan Cheng

New combination chemotherapy of cisplatin with an electron-donating compound for treatment of multiple cancers

• Qinrong Zhang
• Qing-Bin Lu

Lung adenocarcinoma and lung squamous cell carcinoma cancer classification, biomarker identification, and gene expression analysis using overlapping feature selection methods

• Joe W. Chen
• Joseph Dhahbi

Similarities between pandemics and cancer in growth and risk models

• Lode K. J. Vandamme
• Ignace H. J. T. de Hingh
• Paulo R. F. Rocha

Flavonoids increase melanin production and reduce proliferation, migration and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2

• Ponsawan Netcharoensirisuk
• Carla Abrahamian
• Christian Grimm

Convolutional autoencoder based model HistoCAE for segmentation of viable tumor regions in liver whole-slide images

• Mousumi Roy
• Vandana Mukherjee

Low temperature plasma irradiation products of sodium lactate solution that induce cell death on U251SP glioblastoma cells were identified

• Hiromasa Tanaka
• Masaru Hori

CAD systems for colorectal cancer from WSI are still not ready for clinical acceptance

• Sara P. Oliveira
• Pedro C. Neto
• Jaime S. Cardoso

Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma

• Simon Strohmeier

Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells

• Huazhang Wu

Repositioning metformin and propranolol for colorectal and triple negative breast cancers treatment

• L. E. Anselmino
• M. V. Baglioni
• M. Menacho Márquez

Evaluation of wavelength ranges and tissue depth probed by diffuse reflectance spectroscopy for colorectal cancer detection

• Marcelo Saito Nogueira
• Siddra Maryam
• Stefan Andersson-Engels

C. elegans -based chemosensation strategy for the early detection of cancer metabolites in urine samples

• Enrico Lanza
• Martina Di Rocco
• Viola Folli

Detection of colorectal cancer in urine using DNA methylation analysis

• R. D. M. Steenbergen

Learning deep features for dead and living breast cancer cell classification without staining

• Gisela Pattarone
• Laura Acion
• Emmanuel Iarussi

Epidemiological overview of multidimensional chromosomal and genome toxicity of cannabis exposure in congenital anomalies and cancer development

• Albert Stuart Reece
• Gary Kenneth Hulse

Adipose-derived mesenchymal stem cells differentiate into heterogeneous cancer-associated fibroblasts in a stroma-rich xenograft model

• Yoshihiro Miyazaki
• Tatsuya Oda
• Yasuyuki S. Kida

Loss of Parkinson’s susceptibility gene LRRK2 promotes carcinogen-induced lung tumorigenesis

• Chandra Lebovitz
• Nicole Wretham
• Sharon M. Gorski

Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer

• Tadanobu Shimura
• Priyanka Sharma

Differential expression of PD-L1 between primary and metastatic epithelial ovarian cancer and its clinico-pathological correlation

• Sandeep Kumar Parvathareddy
• Abdul K. Siraj
• Khawla S. Al-Kuraya

Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer

• Ryoichi Katsube
• Kazuhiro Noma
• Toshiyoshi Fujiwara

Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning

• Kalifa Manjang
• Shailesh Tripathi
• Frank Emmert-Streib

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts

• Miguel Martin
• Rocio Ramos-Medina
• Sara Lopez-Tarruella

Evidence for improved prognosis of colorectal cancer diagnosed following the detection of iron deficiency anaemia

• Orouba Almilaji
• Sally D. Parry
• Jonathon Snook

CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer

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Prognostic value of prostate volume in non-muscle invasive bladder cancer

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Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies

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-->

	Title	Type
1		journal	26.837 Q1	505	105	304	10805	10951	163	31.23	102.90	44.33
2		journal	17.507 Q1	398	178	590	11546	12604	360	19.83	64.87	41.91
3		journal	11.900 Q1	61	176	453	7513	5933	297	12.27	42.69	43.45
4		journal	10.639 Q1	624	783	1664	20976	26011	1205	13.64	26.79	41.81
5		journal	8.737 Q1	117	457	1105	58854	23888	665	20.66	128.78	41.19
6		journal	8.222 Q1	196	190	525	23895	14728	449	23.31	125.76	38.33
7		journal	7.843 Q1	173	349	1225	6132	9916	523	7.62	17.57	39.66
8		journal	7.760 Q1	241	207	616	11553	8661	459	12.71	55.81	42.61
9		journal	7.522 Q1	144	115	531	11441	12065	413	20.83	99.49	40.48
10		journal	6.348 Q1	163	229	779	6987	7925	489	11.64	30.51	45.08
11		journal	4.986 Q1	387	211	719	2601	4647	510	6.60	12.33	50.21
12		journal	4.950 Q1	79	108	289	4873	3552	176	12.39	45.12	40.77
13		journal	4.665 Q1	132	74	76	6493	1477	75	17.53	87.74	34.58
14		journal	4.640 Q1	25	42	128	1802	959	125	8.13	42.90	35.32
15		journal	4.623 Q1	377	541	2035	19863	19126	1944	9.00	36.72	43.31
16		journal	4.513 Q1	90	111	338	7747	3828	324	9.71	69.79	40.00
17		journal	3.781 Q1	134	138	425	5941	3342	406	6.37	43.05	41.46
18		book series	3.766 Q1	36	18	61	2133	423	61	5.00	118.50	38.18
19		journal	3.728 Q1	117	445	1590	19408	14743	1571	8.71	43.61	42.99
20		journal	3.662 Q1	219	333	1125	11784	8477	975	7.59	35.39	43.05
21		journal	3.468 Q1	498	331	1449	13630	12019	1431	8.08	41.18	42.61
22		journal	3.297 Q1	179	96	745	17871	9343	714	11.64	186.16	39.08
23		journal	3.289 Q1	101	41	153	2275	1284	128	8.13	55.49	39.81
24		journal	3.034 Q1	22	22	56	2883	411	56	7.73	131.05	44.55
25		journal	3.000 Q1	272	448	1331	22747	10155	1182	7.28	50.77	43.44
26		journal	2.928 Q1	9	43	57	1993	754	52	13.23	46.35	40.22
27		journal	2.887 Q1	340	502	1845	15437	8867	1286	4.35	30.75	47.18
28		journal	2.871 Q1	36	134	227	7435	1667	224	6.48	55.49	38.35
29		journal	2.866 Q1	167	85	214	14862	1880	192	6.96	174.85	42.18
30		journal	2.838 Q1	159	155	390	26605	4360	387	10.09	171.65	45.66
31		journal	2.806 Q1	120	307	943	18917	9710	940	9.65	61.62	46.70
32		journal	2.595 Q1	216	310	1277	25474	11444	1252	8.55	82.17	42.85
33		journal	2.578 Q1	175	147	340	7128	2515	334	5.80	48.49	48.60
34		journal	2.501 Q1	245	402	1811	14117	9171	1524	4.66	35.12	43.56
35		journal	2.498 Q1	60	208	742	8307	4147	647	5.86	39.94	44.96
36		journal	2.447 Q1	164	828	3153	48403	26701	3125	7.57	58.46	45.35
37		journal	2.384 Q1	42	103	201	7008	1426	145	6.15	68.04	44.46
38		journal	2.334 Q1	370	315	1443	17364	9801	1437	6.48	55.12	43.92
39		journal	2.270 Q1	199	113	644	5528	3324	631	5.03	48.92	40.46
40		journal	2.249 Q1	48	0	395	0	1632	356	4.46	0.00	0.00
41		journal	2.219 Q1	271	413	1605	29196	6805	1590	3.94	70.69	42.98
42		journal	2.136 Q1	99	90	338	3391	2183	320	6.82	37.68	28.78
43		journal	2.131 Q1	260	429	1584	19420	9422	1500	6.08	45.27	45.98
44		journal	2.127 Q1	17	62	133	4757	556	132	3.40	76.73	43.56
45		journal	2.101 Q1	33	98	330	3652	1201	297	3.30	37.27	51.13
46		journal	1.992 Q1	277	585	1735	15211	6022	1064	3.52	26.00	38.52
47		journal	1.991 Q1	189	288	1177	7319	5323	984	4.41	25.41	43.72
48		journal	1.940 Q1	113	203	659	10551	4100	641	5.42	51.98	44.33
49		journal	1.887 Q1	144	100	264	5734	1596	262	6.48	57.34	43.10
50		journal	1.855 Q1	67	55	243	2653	1386	242	5.54	48.24	46.04

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Covid-19 and cancer care: a review and practical guide to caring for cancer patients in the era of covid-19.

1. Introduction

2. the impact of the covid-19 pandemic on cancer care, 3. covid-19 outcomes in cancer patients, 4. treatment of covid-19 infections in cancer patients, 5. covid-19 infection prevention strategies, 6. conclusions, author contributions, conflicts of interest.

• Peacock, H.M.; Tambuyzer, T.; Verdoodt, F.; Calay, F.; Poirel, H.A.; De Schutter, H.; Francart, J.; Van Damme, N.; Van Eycken, L. Decline and Incomplete Recovery in Cancer Diagnoses during the COVID-19 Pandemic in Belgium: A Year-Long, Population-Level Analysis. ESMO Open 2021 , 6 , 100197. [ Google Scholar ] [ CrossRef ] [ PubMed ]
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Click here to enlarge figure

Therapy	Setting	Recommendation	Evidence
Nirmatrelvir/Ritonavir (Paxlovid)	Nonhospitalized, mild to moderate disease	IN FAVOR, start within 5 days of symptoms onset	A
Remdesivir	Nonhospitalized and hospitalized, mild to severe disease	IN FAVOR, start within 7 days of symptoms onset	B
Monoclonal antibodies	Nonhospitalized, mild to moderate disease	AGAINST	B
Dexamethasone	Nonhospitalized	AGAINST	A
	Hospitalized, requiring oxygen	IN FAVOR	B
Baricitinib	Hospitalized, requiring high-flow oxygen	IN FAVOR, preferred option	B
Tocilizumab	Hospitalized, requiring high-flow oxygen	IN FAVOR, preferred alternative	B
Abatacept	Hospitalized, requiring high-flow oxygen	IN FAVOR, additional alternatives	C
Infliximab	Hospitalized, requiring high-flow oxygen	IN FAVOR, additional alternatives	C
Fluvoxamine	Nonhospitalized, mild to moderate disease	AGAINST	A
Intravenous immunoglobulins	Nonhospitalized, mild to moderate disease	AGAINST	A
Ivermectin	Nonhospitalized, mild to moderate disease	AGAINST	A
Metformin	Nonhospitalized, mild to moderate disease	AGAINST	B

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Claveau, S.; Mahmood, F.; Amir, B.; Kwan, J.J.W.; White, C.; Vipond, J.; Iannattone, L. COVID-19 and Cancer Care: A Review and Practical Guide to Caring for Cancer Patients in the Era of COVID-19. Curr. Oncol. 2024 , 31 , 5330-5343. https://doi.org/10.3390/curroncol31090393

Claveau S, Mahmood F, Amir B, Kwan JJW, White C, Vipond J, Iannattone L. COVID-19 and Cancer Care: A Review and Practical Guide to Caring for Cancer Patients in the Era of COVID-19. Current Oncology . 2024; 31(9):5330-5343. https://doi.org/10.3390/curroncol31090393

Claveau, Simon, Farhan Mahmood, Baraa Amir, Jennifer Jing Wah Kwan, Cheryl White, Joe Vipond, and Lisa Iannattone. 2024. "COVID-19 and Cancer Care: A Review and Practical Guide to Caring for Cancer Patients in the Era of COVID-19" Current Oncology 31, no. 9: 5330-5343. https://doi.org/10.3390/curroncol31090393

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The Crucial Role of Research in Addressing Global Cancer Stigma

September 9, 2024 , by Katie Heley, Robin Vanderpool, Dana Chomenko, Amanda Klein, and Vidya Vedham

Katie Heley, Ph.D., M.P.H., Division of Cancer Control and Population Sciences, National Cancer Institute

Robin Vanderpool, Dr.P.H., Division of Cancer Control and Population Sciences, National Cancer Institute

Dana Chomenko, M.A., P.M.P.,  Contractor, BLH Technologies, Inc. 

Amanda Klein, M.P.H., C.H.E.S., Contractor, Strategix Management 

Vidya Vedham, Ph.D., Center For Global Mental Health Research, National Institute of Mental Health

“…if that person [with cancer] hasn’t had a family…it will be harder to get married to healthy normal people.” ( Eschliman et al., 2024 )  

“Among the community, cancer survivors are perceived as ‘walking dead,’ disabled, and weak.” ( Global Cancer Stigma Research Workshop, 2022 ) 

“The woman [with cancer] becomes a victim of stigma by her family, relatives, colleagues and is judged by her physical appearance. At worst, she is abandoned, most often by her husband, fired from her job, driven into debt to support herself, denied medical insurance, salary increases, and loses her responsibilities, promotion, and benefits when she returns to work.” (Johnson & Samson, 2024 ) 

“People with cancer…the employers find out that they have cancer then they must definitely stop working. Because the disease makes them unable to work, for example, so they cannot do hard work, for example, or cannot meet the assigned quota or target. They are fired.” ( Eschliman et al., 2024 )

Cancer Stigma: Scope and Impact on Cancer Control

As poignantly illustrated by the quotes above – collected from cancer patients, survivors, advocates, and community members around the world – stigma is a complex and powerful social process that involves labeling certain human characteristics as socially undesirable, often associating them with negative stereotypes. This process often leads to a loss of status and discrimination, among other negative consequences, against those who are labeled (4) . Unfortunately, individuals at-risk of cancer, cancer patients and survivors, caregivers, and family members encounter varying levels of stigma throughout their care journey (5) . This stigma can arise from various factors, including public and healthcare provider misconceptions, cultural and religious beliefs, and media portrayals that further reinforce negative stereotypes.

Cancer stigma continues to be a major challenge for cancer prevention and control efforts, exerting profound effects on cancer incidence, morbidity, and mortality worldwide (5) . It can impede preventive health-seeking behaviors, screening, treatment adherence, and care engagement. Individuals affected by cancer stigma often experience guilt, social isolation, and avoidance, which can worsen health outcomes and reduce their quality of life. We believe addressing cancer stigma is critical for improving the health and wellbeing of individuals affected by cancer as well as for enhancing cancer prevention and control efforts broadly. 

The U.S. National Cancer Institute Efforts

Despite its significant impact, cancer stigma remains under-researched, with minimal attention given to the topic, insufficient measurement instruments, and a shortage of evidence-based mitigation interventions. In response, over the past several years, the National Cancer Institute (NCI) has implemented an international workshop, a special issue of a leading cancer journal, and a series of funding opportunities, all aimed at supporting researchers and practitioners in advancing the global field of cancer stigma research.

NCI’s Global Cancer Stigma Research Workshop 

The first of these efforts took place in September 2022 when NCI's Center for Global Health (CGH) and the Division of Cancer Control and Population Sciences (DCCPS) hosted NCI’s Global Cancer Stigma Research Workshop . For this two-day virtual event, we brought together over 100 participants from five continents, including researchers, cancer survivors, advocates, clinicians, and representatives from non-governmental and governmental organizations. Through the workshop, focused on the intersection of cancer and stigma, we aimed to emphasize the impact of stigma on global cancer control; foster the exchange of ideas within the cancer stigma research community; and highlight domestic and global cancer stigma research to identify potential research gaps for stigma measurement and the development of context-specific stigma reduction interventions.

As shown in the figure below, key areas of focus included cancer stigma manifestations and types, drivers and contributors, impacts and consequences, measurement, interventions, and resilience. In addition, workshop participants identified research gaps and priority areas resulting in several calls to action for the cancer stigma research community, including the need to further conceptualize cancer stigma in global contexts; develop and implement inclusive research approaches; expand research methodologies; and promote collaboration among stakeholders.

JNCI Monographs: Global Cancer Stigma: Research, Practice, and Priorities

Building on the momentum from the workshop, we sought to develop a research monograph to further highlight the diverse efforts in cancer stigma research and to allow academic partners, health providers, trainees, advocates, and community members to engage with these ideas. Released in June 2024, a special issue of JNCI Monographs titled Global Cancer Stigma: Research, Practice, and Priorities is a collection of peer-reviewed articles showcasing efforts to understand, measure, and address cancer stigma across global communities – including Vietnam, Nigeria, and Kenya –  as well as to consider identified research gaps and opportunities including:

Conceptualizing Cancer Stigma in Global Contexts : Eschliman et al. report on findings from in-depth interviews in Vietnam and the application of the “What Matters Most” framework, recognizing that achieving and maintaining cultural capabilities, such as staying employed, can alleviate some of the negative effects of stigma.

Measuring Cancer Stigma : Studts et al. focus on the operationalization and measurement of stigma and conclude that mitigating stigma toward individuals with a history of smoking may be critical to ensuring unbiased care and fostering broader health system improvement

Mitigation Strategies : Banerjee et al. report on an adaptation of an empathic communication skills training intervention and the implementation of a pilot feasibility study among oncology clinicians in Nigeria.

Broader Implications and Recommendations : Representatives of the Union for International Cancer Control highlight the need for policy and country-level changes to reduce cancer stigma. 

The efforts highlighted in this special issue illustrate the complexity of studying cancer stigma and the necessity of a multifaceted approach. It is our hope that these articles spark innovative ideas for future research efforts and practice improvements. 

Funding Opportunities

In addition to hosting an international meeting and publishing a special issue, we continue to prioritize related funding opportunities for the extramural research community. Historical efforts include participating in the Fogarty International Center’s funding opportunity (R21, R01) on “Interventions for Stigma Reduction to Improve HIV/AIDS Prevention, Treatment and Care in Low- and Middle- Income Countries”  (LMICs) (2017-present). In fiscal years 2021 and 2023, CGH published a series of administrative supplements ( “NOSI: Administrative Supplement Opportunity to Support Global Cancer Stigma Research” ) to support one-year exploratory research studies to expand the current understanding of cancer stigma, assess its impact on cancer prevention and control, and develop stigma-reduction interventions to improve cancer outcomes in LMICs. Notable among our upcoming efforts is the release of two funding opportunities ( R01 , R21 ) focused on the confluence of HIV stigma and cancer stigma among individuals with a dual diagnosis of HIV and cancer. These cancer stigma-related funding opportunities contribute to our broader goal of cultivating innovative research in global cancer prevention and control. 

Addressing cancer stigma in global communities requires a comprehensive and inclusive approach that encompasses diverse perspectives and strategies. By advancing the understanding, measurement, and mitigation of cancer stigma, the cancer research community can work toward reducing the global cancer burden and promoting health equity, ultimately improving quality of life and survival rates worldwide. We are committed to actively engaging with key stakeholders to drive research and practice in this critical area, ensuring that these efforts are impactful and responsive to the needs of the global communities they serve.

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Mary Lou McDonald speaks publicly for first time about her husband's cancer diagnosis

SINN FÉIN PRESIDENT Mary Lou McDonald has spoken publicly for the first time about her husband Martin’s cancer diagnosis.

McDonald spoke openly this morning during an interview on Virgin Media’s Ireland AM about the difficult year her family has had.

McDonald revealed that her husband Martin Lanigan was diagnosed with colorectal cancer last year, and spent a number of weeks in intensive care in a French hospital.

Lanigan became seriously ill while the couple and their family were on a short break in France, not long after McDonald herself had recovered from a hysterectomy in June 2023.

“Literally between packing the case to come home and arriving at the airport Martin got really, really sick,” McDonald said today.

She continued: ” I didn’t know what it was but I knew it was serious.”

McDonald explained that her husband had to be rushed to hospital in Biarritz where they learned that his bowel had burst.

“They saved his life,” McDonald said.

During surgery, a tumor was found and Lanigan was later given a diagnosis of colorectal cancer. As a result, Lanigan spent several weeks in intensive care in France with McDonald remaining by his side.

“It was one of those moments in life where literally everything got turned upside down,” McDonald said, adding that she worried she would not be able to get her husband home to Ireland.

Lanigan’s prognosis is now positive, McDonald said.

After the family were able to return to Ireland, McDonald appeared on Ireland AM in September where she revealed that she had a hysterectomy a few months earlier.

Sinn Fein leader @MaryLouMcDonald on the show this morning discussing the recent passing of her father, as well as her husband's cancer diagnosis while she was recovering from a hysterectomy last year. #IrelandAM pic.twitter.com/fctJRZ1jfD — Ireland AM (@IrelandAMVMTV) September 12, 2024

At the time she mentioned that she managed to get away on holiday during her recovery, but she has not spoken publicly about her husband’s health difficulties until now.

“At that stage my actual concern was for him… I was still trying to process what does this mean,” McDonald said today.

Separately, last month McDonald’s father Patrick ‘Paddy’ McDonald passed away.

Speaking about it today, McDonald said she’s had a “very eventful” and “tough year”.

“We buried my father five weeks ago. Anyone who has lost their Da knows that it’s a very hard thing. It’s a complete game change.

“I love my Da but we had a complicated relationship, he was a complicated person,” McDonald said, explaining that her parents were separated for most of her life.

“It’s kind of a strange thing, you lose your father so you have the grief of that but it’s not a straightforward grief if that makes sense,” McDonald said.

McDonald and her husband Martin have been married since 1996. The couple have two children together, Gearoid and Iseult.

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Cancer: An unknown territory; rethinking before going ahead

Cancer is a disease of altered signaling and metabolism, causing uncontrolled division and survival of transformed cells. A host of molecules, factors, and conditions have been designated as underlying causes for the inception and progression of the disease. An enormous amount of data is available, system-wide interaction networks of the genes and proteins are generated over the years and have now reached up to a level of saturation, where we need to shift our focus to the more advanced and comprehensive methods and approaches of data analysis and visualization. Even with the availability of enormous literature on this one of the most pressing pathological conditions, a successful cure of the disease seems to be obscure. New treatment plans, like immunotherapy and precision medicine, are being employed for different studies. Nevertheless, their actual benefits to the patients would be known only after the evaluation of clinical data over the next few years. Therefore, we need to look at few fundamental challenges that should be addressed in more depth before we could devise better, rigorous, and comprehensive treatment plans and may successfully reach a possible cure of the disease. This article aims at bringing attention towards some fundamental gaps in our approach towards the disease that leads to failure in devising successful therapeutics.

Graphical abstract

Introduction

Cancers are one of the most devastating classes of human pathologies, presenting the versatile range of hallmark clinical features and leading to millions of deaths each year around the globe. These groups of maladies constitute more than a hundred genetically diverse conditions sharing several commonalities in the molecular mechanisms and metabolic alterations among themselves. 1 , 2 The direct involvement of the tissue microenvironment and inflammatory changes on the tumor growth survival is well-established. 3 , 4 However, a clear understanding of the underlying causes and factors is still elusive and requires more research. A plethora of genetic mutations has been reported that could end up in the transformation of the normal human cells leading to the genesis of tumor and development of cancer. 5 , 6 In the past, a variety of scientific and technological approaches have been tried in order to understand, define, investigate, and challenge these extensively dreadful forms of diseases. Various approaches applied in oncological research include genetic, molecular, biochemical, biophysical, immunological, genomic, proteomic, systems and computational biology, etc. However, none of these have sufficed the needs to devise successful treatment strategies so far. 7 The area of the oncological research is well-documented but evolving in a way that researchers and clinicians find it difficult to get updated and informed of the new information and advancements most of the time. Therefore, the field requires a continuous assessment of the new developments and analyses of the lacunae present within persisting knowledge.

Understanding cancer: do we need to change the approach?

Although a vast volume of data has accumulated over the decades of research, we at the present stage of scientific and technological advancements still lack a sound understanding of these debilitating conditions that leads to millions of deaths every year. In fact, before classifying the cancers as classical disease conditions, we need to understand that these could be considered as a phenomenon of sequential alteration at molecular, cellular, tissue, and organ levels affecting the whole physiology of the organism. We cannot ignore the fact that the inception of the disease is neither caused necessarily by some external agents nor is potentially associated with the dysfunction of any specific organ, as occurs in many other disease classes. In simpler terms, cancer could be caused by multiple kinds of disorders in the highly ordered cellular physiological systems. 8 The onset of the disease is still the most intriguing part of the oncology, that we are far from understanding. 9 Enormous data has accumulated showing multiple kinds of physical, chemical, biological, genetic, and environmental factors leading to the transformation phenomenon. However, unfortunately, all these reports have just led us to the tip of the iceberg. We are yet to get a proper understanding of the onset of the disease, and until we get the insights of the initiation, we could not find the actual targets for delivering the treatments.

The past century of scientific research has given us a detailed picture of primary, secondary, and tertiary changes associated with these conditions. However, the hunt to get point zero is still on, and more efforts are needed to reach right at the origin of the disease. The reason behind raising the issue of the origin of cancer is that the primary reasons behind not being able to crack the codes of this century-old problem could be our ‘top-down’ approach that works on providing symptomatic relieves from the disease conditions. We have confined our research most of the time in designing and improving the methods and strategies of arresting the growth of transformed tumor cell mass. Unfortunately, we have shifted our objectives primarily towards devising newer preventive measures rather than looking for the origin of the disease. The reason behind this shift could also be due to the continuous failure of scientists in delivering the results in ‘bottom-up’ approaches where more focus should be given to the genesis of cancer, instead of ways to cut down resources for its sustenance or forcibly inducing the cell death pathways. We must also look for the evolutionary perspectives of the origin, sustenance, and development of cancer-like conditions over the eons to understand why and how selection forces have let these processes to settle down with our current set of physiological paradigms. In fact, we need a comprehensive multi-dimensional approach to clearly investigate and understand the disease and thus to deliver more effective and successful treatment strategies.

Can we look at cancer through an evolutionists prism?

In the views of an evolutionist, the development of cancers seems to be driven by the continuous acquisition of numerous somatic mutations to best fit into a continuously changing and challenging microenvironment. 10 Spontaneous mutation-driven evolution of tumor cells itself is one significant barrier before us that tends to provide them the resistance against the drugs and treatment plans. 11 , 12 The dialectical interrelations among different physiological pathways and their dynamic interaction networks have further complexicized our molecular understanding of the disease. The uniqueness of each cancer type and diversity among the tumors additionally raise multifold challenges in understanding this terrible and complicated disease and devising treatment strategies to fight against it. Additional adversities are added by their unique and yet to be understood capabilities of evading the host immune responses, thereby limiting the inherent tendency of the body to fight back with these odious masses of tissues. In-depth knowledge of underlying pathways and mechanisms behind the origin, transformation, and development of cancer may provide us therapeutic advantages in switching to a ‘bottom-up’ approach that will hand us an edge in targeting the most underlying molecular pathways. The past century has seen tremendous methodological and technological advancements in the diagnosis, and treatment of various types of cancers.

Where do we stand?

Cancer cells are a kind of parasitic population of our own cells that resides in our body, utilizing the nutrition and supplementation of normal cells. They have learned to hijack the metabolic pathways and exploit the tissue microenvironment for their growth, sustenance, and progression. They have acquired the art of camouflage and thus evade our army of immune cells of various kinds. Their ability to mutate and evolve within the population further complicates the condition, which makes it hard for researchers and scientists to understand how to target these unwelcome populations of our cells, which otherwise may lead to enormous complications in the end. One school of thought finds possible parallelism between developmental processes and the origin of cancer; however, more support on the notion is needed. Thousands of studies are conducted every year with new findings and solutions of the disease advancing our present knowledge about the disease. However, the disease is still growing with an increased pace and turns out to be the leading cause of mortality in many developed countries. Despite acquiring enormous knowledge on the etiology, causes, and effects of cancer inside the body, unfortunately, we could not have successfully devised too many methods to curb the disease condition and provide proper relief to the patients suffering from this one of the most challenging puzzles of the medical sciences. 13

In most cases, a treatment plan for the majority of the cancer types remains limited to surgical removal, chemotherapeutic targeting, high-intensity photon-beam radiotherapy, hormonal therapy, and modern-day immunotherapy depending upon their complexity, stage, and localization. 14 All patients suffering from one type of cancer, despite being genetically diverse, typically receive a similar treatment plan. This diversity among the cell population of the same tumor mass leads to the attainment of the drug resistance in the transformed cells. Also, the lack of real-time monitoring of the ongoing treatment further worsens the situation. Unfortunately, due to the limitations of resources and diagnostic tools and a lack of personalized treatment strategies, in addition to the highly diverse genetic makeup of tumor populations, many times, treatments do not meet the expectations. Here, a few major characteristic features of the disease, which mostly intrigues our understanding and raise new challenges in therapeutics, are discussed in detail.

Extreme genetic diversity

Intratumor heterogeneity, i.e., extreme genetic diversity among cell populations residing in the same tumor mass, leads to Darwinian principles and natural selection forces to work on it and establish a more robust variety of cancer cells. 15 This heterogeneity increases drug resistance and thus poses a great therapeutic challenge before clinicians in developing cancer treatment plans, which therefore led to the evolution of the idea of personalized medicines. 16 , 17 Increased application of pharmacogenetics, i.e., understanding the genetics of cancer by molecular profiling of the disease cells, identification of the mutation associated with the given cancer type in an individual patient is nowadays used for targeting specific genes or proteins driving the growth of cancer. 18 The advent of next-generation sequencing, array methods, and other mathematical or computational tools have tremendously driven the progress of this revolutionary approach to target the cancer cells. 19 , 20 , 21 However, the application of personalized medicines is very limited at present due to multiple reasons. The high cost of cancer genomics is one major reason behind not opting for precision medicine at a larger scale. 22 , 23 Possibly, the diversity at the genetic level in these diseases and the inability to afford for personalized treatment strategies is one of the major underlying causes of failures in the treatment of cancer. Therefore, more efforts are required in this direction so that precision medicines can be used in other cases also.

Looking at various genes independently may not be an ideal way to understand the plethora of changes occurring while a cell transforms, and the tumor is formed; therefore, a broad landscape of genome-wide alteration may provide a better understanding of the genetics of cancer. 24 The increase in genetic diversity, in recent years, has also been linked with a phenomenon called genome or karyotype chaos, primarily caused due to largescale changes creating new genomic codes for the systemic inheritance, which in turn provide increased chances of adaptation and survival at the cellular and organismal level. 25 , 26 An increasing number of sequencing-based studies have hypothesized for the possibility of a more pivotal influence of the genome topology over the tumor diversity in comparison to the independent gene profiles. 27 ‘Chromothripsis’ is an umbrella term used to indicate multiple kinds of chromosomal rearrangements happening under crisis, which may include: chromosomal aneuploidy, chromoplexy, chromoanagenesis, etc. 28 Clonal or constitutional aneuploidy is another less understood phenomenon reported in many cancer types, which may also act as a heterogeneous agent affecting the emergence and evolution of cancer. 29 , 30 These terms are not very familiar to oncology research as most of these processes were overlooked for years, while scientists were more inclined towards the genetic theory of cancer, which has largely failed to address many fundamental questions of evolution, development, and diversity of cancer. 29

An opaque connection between developmental biology and cancer

Do cancers have any developmental correlation; and if the disease could be transferred from one generation to the other? These are a few more questions, which are not understood in detail. At face values, development entails order, whereas cancer represents an example of extreme disorder. Interestingly, such a distinctive origin and progression of the two processes define their dichotomous correlation. When Prof. Mintz referred cancer as an error of development, possibly she took into account the proliferative capabilities of the cells, which could be compared with that of early-stage stem cell populations during organism development. 31 However, the two processes are at considerably far distant ends of the same spectrum of diversification. On the one hand, development is a process that originates from a single zygotic cell that diversifies into multiple cell types via a tightly controlled epigenetic regulation. Contrarily, cancer is a slow and continuous progression towards a highly similar cell population at late malignancy stages from the early benign tissue masses, which are highly diverse. 32 Many similar epigenetic signatures could be found among both the developmental stem cells and cancer progenitors, marking the parallelism between both processes. 33 There is also an ambiguity upon the idea of inheritance of cancer-causing disease mutations, which may or may not be transferred to progenies. Possibly, some of the mutations are inherited, while many of the cases are acquired because of replication errors during the multiplication of cells.

Many overlapping clinical features among multiple developmental disorders and cancer predisposition could be another possible connecting link between the two processes, putting forward an idea of cancer being a disease of accumulating developmental errors. 32 , 34 Highly precise control over spatial and temporal switching ON/OFF of a well-orchestrated gene network is another binding feature that connects the two distinct biological phenomena. 35 Owing to these similarities, many scientists are now exploiting both types of disease models to understand each other. 36 In the coming years, a more rigorous shift in approach towards studying cancer as a disease of erroneous development is needed. This change of approach may educate us more about the origin and development of this highly diverse disease.

Hiding away from innate immunity

Another major challenge that scientists have faced over the years is the extreme disguise or hiding of cancer cells from our immune system that are expected to identify and kill the cancer cells. 37 The specific mechanisms of how precisely cancer cells evade our immune system and what could be the possible strategies to target these aberrant cells of our own body is still an enigma of modern-day biology. 38 However, targeting neoantigens is a possible strategy that is under consideration with huge expectations, as these newly evolved peptides provide immune cells an opportunity to target cells, which otherwise remain in disguise. Some scientists believe that it is a dynamic head to head clash between neoantigen expressing cancer cells and the immune surveillance that poses a quest of survival before cancer cells. 39 , 40 The selection pressure mounted, therefore, leads to mutations in such a way that they start tricking and escaping our own immune cells. 41 Additionally, the disease cells, by expressing some specific antigens or modifying the tumor environment, acquire: the tendency or ability to overpower the normal immune responses inside the body. 42 , 43

Cancer immune surveillance has remained a long-standing topic of debate that has both proponents and opponents. It is hard to answer whether our immune system promotes or suppresses, or it directly ignores the mutated or transformed cells. 44 , 45 Interestingly, over the years, it has been suggested that transformed cells themselves sculpt the immune cells via a process called immune-editing in such a way that they help them in skipping their molecular identification and elimination and establishing a Darwinian selection. 46 Few reports indicating latent metastasis after decades of surgical removal of the primary tumor is another question that, if answered, may probably help us better understand how the cells conceal themselves from possible immune attacks. 47 Currently, we are quickly moving towards modern immunotherapy-based treatment methods, which are providing very positive results indicating a better future of these strategies towards cancer therapeutics. 48 , 49 Chimeric antigen receptor (CAR)-T cells were the first line of treatment based on immune modulation, which successfully initiates a ferocious assault on cancer cells. The clinical trials have shown enthusiastic results in the past, but at this point of time, we cannot predict the future of these treatment plans. 50

We should not underestimate the art of camouflage acquired by cancer cells over a long period of evolution. Instead, we must undermine the evolutionary relations between cancer cells and different types of immune cells. We need to find out the possible diversions of the eukaryotic transformed cells when in the history of evolution, they have started deceiving our own immunity. We need to investigate the history of life to find out the answers to the present-day questions in order to find solutions for the future. Most of the physiological hallmarks defined for the cancers have their own evolutionary significance, and their retention by the selection forces might have their own significance and implications in the process of evolution.

A controversy: one target multiple bullets; or multiple targets with a common bullet?

A large fraction of research to date has focused on identifying the multimodal driving factors of the disease. Nevertheless, when the causative factors, genes, and pathways are subjected to the possibilities of druggability, most of these have shown limitations of multiple types. One major problem with most of the molecular targets is the toxicity generated due to their modulations, as most of these are somehow part of one or multiple molecular pathways. 51 , 52 Several articles have been published in recent years covering various aspects of the disease in detail. Thus, here in the present article, the primary focus is to highlight the gaps in postulation and understanding of the disease. Cancer has remained an unsolved puzzle over the years, despite having an extensive knowledge base of genes, proteins, and pathways affected during the pathogenesis. The primary cause of failure for most of the hypotheses could be overlooking many vital topics and defining factors in the disease etiology. What remains crucial is a rethinking of the already available knowledge and revisiting the persisting treatment methodologies and therapeutic approaches (see Fig. 1 ). It is obvious to say that an overwhelming amount of data is present and is enough to spend days or months to understand the complicated networks and models that can be generated using various available tools out of this vast literature available over online resources.

An overview of known, unknown, available therapeutics, and future directions of the cancer therapeutics. The top panel shows the fundamental underlying causes of cancer, including major risk factors, involved mechanisms and currently available strategies to devise treatments and therapeutic strategies. The central part shows a few representative types of cancer among many occurring around the globe and leading to a very high number of deaths. The lower subsections show the treatment methodologies adopted around the world to curb the disease progression. In contrast, the few most challenging and less-understood complexities of tumor biology are indicated in the lowermost subsection of the figure. Fig. 1 was prepared using a few templates from Servier Medical Art by Servier ( http://smart.servier.com/ ), which is licensed under a Creative Commons Attribution 3.0 Unported License.

The exploitation of the available knowledge needs multimodal approaches, forming multidisciplinary teams with experts from different fields collaborating with and complementing each other. The use of computational tools and system biology approaches may further benefit the field with faster and more accurate calculations and predictions, saving lots of money and time that is spent in a large number of unsuccessful clinical trials. A large amount of biochemical and genomic data is present; however, the focus should be shifted now towards the transformation of these research into clinical applications. The majority of the data remain limited to the publications only and could never generate any therapeutic benefit. Many drugs proposed through these studies fail in successive phases of clinical trials, either because of their limited effects on curbing the disease or due to high toxicity profiles. In the end, a tiny fraction of drugs proposed every year get into clinics and could be utilized for treatment purposes. The primary reasons behind the failure of many drugs are because of the negligence of specific facts associated with this multifactorial disease.

Regulating the cell cycle progression, inducing apoptosis, managing the tissue microenvironment, modulation of the immune system, and cutting the sources of nutrition and growth, all at a time could be near to impossible for most of the drugs, which are currently in practice or under clinical trials. Even if we consider any drug, with the least of the possibilities to have most of the characteristics mentioned above, the more significant challenge would be its delivery to the specific tissues. Targeted delivery of drugs is another highly frustrating challenge faced by researchers and clinicians. None of the approaches proposed to date for the drug delivery to the affected site has stood with the promises and leads to the toxicity and collateral adversities, as is seen in patients undergoing chemotherapy. Due to this multifaceted nature of cancer development and progression, we ultimately land in an unfortunate situation of firing multiple rounds of bullets (chemotherapy, radiation, surgical removal, and immunotherapy, etc.) all at a time. The lack of a broader understanding of the pathological condition leads to overall physiological and psychological distress to the patients.

Surgical removal of affected body parts or heavy doses of chemotherapeutic drugs and high-energy radiations may cause physical disfigurements, followed by weakening of the immunity and deterioration of the body mass. All these combinedly affects the psychology of the patients with the highest of the will power. Family members of the patients may also get frustrated due to the very long treatment process and follow-ups. Also, most of the newly developed methodologies, like immunotherapy, cancer genomics, and precision medicine, are too costly to be afforded by most of the patients in underdeveloped and developing countries. Most of the cases of these diseases do not present any noticeable symptoms and remain undetected in earlier stages, and when detected, leave patients and doctors with minimal palliative options to choose and start the treatment. Diagnosis of the pathological symptoms at a very late stage is another major challenge that needs to be addressed with high priority. In fact, many things are possibly required for the consideration of the researchers, clinical scientists, and doctors.

Conclusions: the road ahead

Cancer has remained one of the significant health issues for long. Description of the disease could be found in some of the ancient literature of Indian and Chinese medicines. The ancient scholars and clinicians suggested different treatment strategies. It could not be accurately predicted how effective these treatment plans were; although their applications in the modern age medicines cannot be neglected. In the past century, efforts have intensified exponentially in all parts of the world to address the common health problems and diseases associated with such conditions. Many of the endemics have been cured completely. Most of the deadly infectious diseases leading to mass death have been understood and have possible cures around the corner. Several are still under investigation and may get some solutions in the past. In between all these advancements, one major class of human diseases, cancer that is neither acute in origin nor contagious in the spread, remain uncured up to a more considerable extent. Enormous hopes have been ignited from time to time by the development of multiple promising drugs, methods of their targeted delivery, and the evolution of novel treatment strategies, like immunotherapy, in the past.

All the strategies developed so far, and the drugs approved until now have their own limitations and toxicities associated with their use. Nevertheless, due to the lack of more sophisticated ways of treatments, the patients suffering from the advanced terminal stages of the disease usually are left with very few options to live with. Several new treatment plans are underway and may need a decade or more to be available for patients of developing countries at an affordable cost. Most of the research conducted around the world is now limited to finding ways of trimming away large branches (symptoms) of a tree (cancer), which may further grow and proliferate at new sites. The knowledge of the point of origin of the tree and ways to cut it from the bottom is still missing and needs extensive work. The field may need a complete turnaround in the approaches of looking at the disease in order to find proper solutions. It is hard at present to predict how much time we still require in reaching a definitive solution. However, yes, there always remains a hope, and we must follow it.

Conflict of Interests

The author declares no competing interests.

Acknowledgements

The author would like to thank the Central University of Rajasthan for providing basic requirements during the preparation of the manuscript. The author also appreciates Servier ( http://smart.servier.com/ ) for providing templates for the preparation of medical illustrations under Creative Commons Attribution 3.0 Unported License.

Peer review under responsibility of Chongqing Medical University.

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The introduction should provide a brief overview of the background and rationale for the study. It is not necessary to cite all of the background literature in the introduction. Brief reference to the most pertinent articles generally suffices to acquaint the reader with the findings of others in the field and with the problem or question that the investigation addresses.

Materials and Methods

Explanation of the experimental methods should be adequate for repetition by qualified investigators. Authors are encouraged to publish the step-by-step protocol(s) used in their study at protocols.io and then include the unique digital object identifier(s) (DOI) in the Materials and Methods. Please see Improving Reproducibility for more information.

Procedures that have been fully described in detail in a previous publication need not be described in detail but rather cited with appropriate references and details of any modifications to the procedure. New procedures and substantially modified previously published procedures must be described in detail.

If any experiments or analyses were outsourced to an institutional core facility or external service provider, this must be stated in the Materials and Methods along with the name of the provider. If possible, the methodological details of the work conducted by the provider should be included in the manuscript, or a suitable reference cited.

The sources of all reagents and tools used should be provided. Any commercial product that is mentioned should include the name of the manufacturer and catalog number. Authors are strongly encouraged to include a unique searchable Research Resource Identifier (RRID), as assigned by the Resource Identification Initiative, for each relevant reagent, tool, and core facility used. Please see Improving Reproducibility for more information. If statistical analysis was performed as part of the study, please include a Statistical Analysis subsection. A Data Availability Statement must be present at the end of the Materials and Methods in a "Data Availability" subsection.

Include a concise summary of the data presented in all display items (figures and tables). Excessive elaboration of data shown in display items should be avoided.

The data should be interpreted concisely without repeating material already presented in the Results section. Speculation is permissible, but it must be well founded, and discussion of the wider implications of the findings is encouraged.

Acknowledgments

Include funding information and the names of others contributing to the work who are not identified as authors. This should include any people, services, or generative artificial intelligence technologies that contributed to the generation of the manuscript.

Number the references in the order of their first mention in the text; cite only the number assigned to the reference. The reference list should be limited to only those citations essential to the presentation. Before submission of the manuscript, authors should verify the accuracy of all references and check that all references have been cited in the text. For manuscripts with more than 6 authors, the names of the first 6 authors must be listed, followed by " et al. " For manuscripts with 6 or fewer authors, all authors should be listed. Please note that although example references are shown below, a manuscript’s references need not be formatted according to journal style prior to submission.

Reference examples:

Data Availability Statement

All original research must contain a Data Availability Statement describing how readers may obtain the data acquired and/or used in the study. If there are any limitations on availability, these must be explained. Please see Data for details of the AACR journals’ data availability requirements.

Below are example statements for various scenarios. If different datasets used in the study have different data availability terms, please combine appropriate statements, and specify the datasets for which the different terms of availability apply. The Data Availability Statement should be placed at the end of the Materials and Methods (or Methods) section in its own subsection titled "Data Availability."

Data were generated by the authors and deposited in a repository

The data generated in this study are publicly available in [repository name(s)] at [list one or more hyperlinked codes].

Examples: The data generated in this study are publicly available in Gene Expression Omnibus (GEO) at GSE158739 and GSE158812 .

The data generated in this study are publicly available in Genbank at MT006230 and in Gene Expression Omnibus (GEO) at GSE144569 .

Data were generated by the authors and available on request (permitted only for data types for which a community-recognized, structured repository does not exist)

The data generated in this study are available upon request from the corresponding author.

Data were generated by the authors and included in the article

The data generated in this study are available within the article and its supplementary data files.

Note: This statement is only appropriate if the raw data is available in the article or supplementary data files. Plots of data (even individual data points), images displayed in figures, or summary tabular data do not qualify as data included in the article. In these cases, the authors should instead state whether the raw data is available in a suitable repository or on request from the corresponding author.

Raw data were generated in a core facility (and may be unavailable) but processed data are available from the authors

Raw data for this study were generated at [facility name]. Derived data supporting the findings of this study are available from the corresponding author upon request.

Data were generated by the authors but are not publicly available for declared legitimate reason(s)

The data generated in this study are not publicly available due to [describe reasons for restriction such as information that could compromise patient privacy or consent] but are available upon reasonable request from the corresponding author.

Publicly available data generated by others were used by the authors

The data analyzed in this study were obtained from [repository name(s)] at [list one or more hyperlinked codes or urls].

The data that support the findings of this study are available in [repository name(s)] at [list one or more hyperlinked codes]. These data were derived from the following public domain resources: [list resources and hyperlinked codes]

Examples: The data analyzed in this study were obtained from Gene Expression Omnibus (GEO) at GSE22396 , GSE124857 , and GSE124731 .

The data analyzed in this study were obtained from figshare at https://doi.org/10.6084/m9.figshare.12280541.v4 .

Data generated by others were used under license by the authors

The data analyzed in this study are available from [third party name]. Restrictions apply to the availability of these data, which were used under license for this study. Data are available from the authors upon reasonable request with the permission of [third party name].

No data was generated or analyzed in the reported study

Data sharing is not applicable to this article as no data were created or analyzed in this study.

Examples of Combined Data Availability Statements

The data generated in this study are available within the article and its supplementary data files. Expression profile data analyzed in this study were obtained from Gene Expression Omnibus (GEO) at GSE22396 , GSE124857 , and GSE124731 .

The sequence data generated in this study are publicly available in Genbank at MT006230 , in Gene Expression Omnibus (GEO) at GSE144569 , and within the article and its supplementary data files. The data from the Broad Institute’s Cancer Dependency Map project that were analyzed in this study were obtained from figshare at https://doi.org/10.6084/m9.figshare.12280541.v4 .

The human sequence data generated in this study are not publicly available due to patient privacy requirements but are available upon reasonable request from the corresponding author. Other data generated in this study are available within the article and its supplementary data files.

Display Items

A summary of the data should be provided in the text with a callout to the table. Tabular data should not duplicate data already presented in detail in the text. Unnecessary columns of data that can easily be derived from other data in the table should not be included. Large groups of individual values should be avoided; instead, these should be averaged and an appropriate designation of the dispersion, such as standard deviation or standard error, should be included. Authors are obligated to indicate the significance of their observations by appropriate statistical analysis.

Every table must have a descriptive title and enough explanatory information so the reader can understand the data without reference to the text. Table titles should be short and to the point and should generally not include references. Each column must carry an appropriate heading and, if measurements are given, the units should be given with the column heading. Number tables using Arabic numerals; table footnotes should be indicated with lower-case alphabetical letters: a, b, c, etc. Include a note after the footnotes in which all abbreviations used in the table that have not been used in the text are explained. Complex or large tables should be uploaded in a tabular data file format as supplementary data.

Tables should not be included as part of a figure. Authors are discouraged from submitting tables that have been previously published, even with permission.

Please see Statistics and Images for important editorial policy information related to figures. Figures should be used when salient points need illustration for better comprehension by the reader. Figures must be submitted in their final design and color format. All figures that the author intends to have printed in black and white should be supplied in this format so that editors and reviewers can properly evaluate the presentation of the data. For initial submission only, figures may be supplied in pdf, jpg or Word document format and should be on the same page as the legend, either at the end of the manuscript file or embedded in the text near the figure callout. See File Types for details on the allowable file types for revised manuscripts.

Each figure must be accompanied by a figure legend consisting of a short title sentence followed by a description of the figure and the data shown. If the figure consists of multiple panels, each panel should be labeled and described in the legend. Figure legends must include the number of technical and biological replicates performed for the experiment(s) depicted. Legends should not repeat details present in the main text and should generally not include references. Stains and original magnifications should be listed where applicable. Define all symbols and adequately identify all parts of the figure necessary for interpretation. Abbreviations explained in the main text of the manuscript need not be redefined in the figure legend.

Figures must be cited and numbered in the order in which they appear in the text. For revised submissions, all figure legends should be listed together in one section (Figure Legends) directly preceding the appearance of the figures in the manuscript. Ensure that both legends and figures are numbered and match up appropriately.

When graphs are reduced to the size of a single column (7.94 cm / 3.125 in), the text in the graph must be no smaller than 6 pt and no larger than 12 pt, and all symbols must be discernible. In the published form, the minimum thickness of lines (rules) used to present drawn art is 0.5 point. If a drawn image will be reduced in size for publication, the lines used to draw the original art must be thick enough to be reduced and still meet the minimum requirement. Lines thinner than 0.5 point thickness may be completely lost if an image is reduced in size.

Best practices for choice of graph type

• Reserve bar charts for presentation of data such as counts and lengths.
• Use a line graph to display and connect related data points and a bar graph for unrelated data points.
• Sample data is best displayed by plotting individual data points when sample numbers are small. Use a box plot, violin plot, or bean plot for larger sample sizes and to show data distributions. See Statistics for guidelines on sample sizes. A free tool for plotting sample data and generating an EPS file for incorporation into figures is available at http://boxplot.tyerslab.com .
• A pie chart is effective for showing data trends, but, if it is important to provide quantitative comparisons, a bar graph may be preferable.

Best practices for graph design

• Avoid the use of patterned fills. These add visual clutter and impede interpretation. Use black, up to four shades of gray, and white to provide six alternative encodings; or use color if more encodings are required.
• Always use distinct colors and avoid the use of red and green for contrast.
• Avoid background shading.
• Display only the left and bottom axes unless a top and/or right axis is absolutely necessary.
• Axes labels should not extend beyond the axes lines and must include the name and units of the parameter measured.
• Consider whether related data plotted in multiple graphs can and should be shown in a single graph.
• Remove unnecessary tick marks and grid lines. Use grid lines only when necessary and make sure they have substantially less visual prominence than the data and axes lines.
• Avoid axes breaks. These can mask important differences in the data.
• Open symbols, particularly circles, are most appropriate for plotting high-density data points that overlap.

Best practices for images

• When images are related to one another or should be compared, group them together with narrow bands of white space between them. If the image background is close to white, use lines for separation.
• Symbols, arrows, letters, and scale bars overlying the image should strongly contrast with the background so as to be clearly visible and are best provided on a separate layer from the underlying image in a layered image file.
• Single channel fluorescence images are best displayed in grayscale so that intensity differences can be discerned more accurately. Avoid the use of red, which is particularly problematic in this regard.

Figures should be original. Authors are discouraged from submitting figures that have been previously published, even with permission. If use of a previously published figure is necessary, the author must apply for written permission from the copyright holder and supply confirmation of the permission grant before publication.

Supplementary Data

Supplementary data is intended to provide additional substantive information that is directly relevant to the article content but not essential for understanding the conclusions. The article must stand on its own merits and be complete and self-explanatory without the supplementary data. Additional text, such as supplementary results or discussion, is not acceptable and should be included in the main article. Supplementary data should be equal in quality and presentation to material within the main article. The supplementary data are subject to the same scientific standards of peer review and are included at the discretion of the editor. Each supplementary item/file must be referenced at least once in the main article text at an appropriate point. Supplementary items should be referred to in a similar manner to that used for a table or figure in the body of the manuscript, for example, "(Supplementary Fig. S1)" or "(Table 3 and Supplementary Table S3)." Each supplementary file should be accompanied by a brief description to be entered in the submission system when uploading the files. The description will be posted online to communicate the contents of the file and to aid in online indexing. Supplementary figures must include full legends (preferably on the same page as the figure) and tables should include captions.

General Guidelines on Acceptability

• Supplementary data should fall within the conceptual scope of the main manuscript but not extend beyond it. Preliminary data that simply extend the scope of the study should not be included.
• Supplementary material should not repeat information that is already included in the main manuscript.
• Data that have been previously published are not acceptable.
• Supplementary data may also be that which cannot be included in the main version of the manuscript due to space constraints (e.g., limits placed on the number of figures and tables allowed in an article) or format restrictions.
• Figures and tables
• More detailed materials and methods than can be included in the body of the article, but the main text should contain sufficient methodology for an experienced investigator to replicate the experiments
• Electronic multimedia files (e.g., video, audio, or animation)
• Database information
• Three-dimensional structures/images, sequence alignments, and data sets that are very large

The following file types are acceptable file formats for the main manuscript files:

• Manuscript files: Word (doc, docx), Encapsulated Postscript (eps), Rich Text Format (rtf), or pdf (accepted for initial submissions only)
• Graphics files: eps, tiff, ai, psd, png, ps, or jpg (accepted for initial submissions only). Powerpoint (ppt, pptx) files are discouraged but may be acceptable. Color images should be supplied in RGB.

For supplementary data the following file types are preferable: pdf, doc, docx, txt, xls, xlsx, xml, png, avi, mov, mp4, mp3 and zip. Other file types may be acceptable but please contact the journal editorial office.

Terminology and Abbreviations

For information on gene and protein nomenclature and formatting, please see Gene Nomenclature .

Generic names of drugs are preferred. To help identify compounds that may not be recognized by their generic name, the brand name may be included at first mention only. If a non-U.S. proprietary name is used, the name of the comparable U.S. product should be given. When there is no generic name for a drug, authors should give the chemical name or formula or a description of the active ingredients. Authors should refer to the formally adopted generic names listed in the current edition of USAN and the USP Dictionary of Drug Names.

Abbreviations are in general a hindrance to readers in fields other than that of the author(s), to abstractors, and to scientists whose primary language is not English. Authors should limit their use. See our brief list of Standard Abbreviations that may be used without explanation (e.g., DNA). All abbreviations not on this list must be spelled out at first mention in both the abstract and the text. Single words (e.g., melanoma, folate, vincristine) should not be abbreviated, nor should abbreviations be used for individual types of cancer or other diseases that consist of two words (e.g., prostate cancer or breast cancer).

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