ArticleProceedings of the National Academy of Sciences of the United States of America2014
Tug-of-war between driver and passenger mutations in cancer and other adaptive processes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival.Scientific reports · 2015Pooled it
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- Global Geo-Pharmacogenomics: Environmental Mutational Signatures Drive Population-Level Heterogeneity in Anticancer Drug Response.Journal of xenobiotics · 2026Article
- Linking somatic mutations in cancer to the electronic properties of DNA.BMC genomics · 2026Article
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- Sinonasal Nonkeratinizing Squamous Cell Carcinoma with Synchronous Presence of HPV-High Risk and MKRN1::BRAF Fusion.Head and neck pathology · 2026Article
- Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations.International journal of molecular sciences · 2025Article
- Synergistic epistasis among cancer drivers can rescue early tumors from the accumulation of deleterious passengers.PLoS computational biology · 2024Article
- Exploring FGFR3 Mutations in the Male Germline: Implications for Clonal Germline Expansions and Paternal Age-Related Dysplasias.Genome biology and evolution · 2024Article
- A dynamical limit to evolutionary adaptation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Paralog dispensability shapes homozygous deletion patterns in tumor genomes.Molecular systems biology · 2023Article
- Spatial exclusion leads to "tug-of-war" ecological dynamics between competing species within microchannels.PLoS computational biology · 2023Article
- Reuniting philosophy and science to advance cancer research.Biological reviews of the Cambridge Philosophical Society · 2023Article
- Modeling the Role of Immune Cell Conversion in the Tumor-Immune Microenvironment.Bulletin of mathematical biology · 2023Article
- A dynamical limit to evolutionary adaptation.bioRxiv : the preprint server for biology · 2023Article
- Article
- Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations.Journal of personalized medicine · 2023Review
- Agent-based methods facilitate integrative science in cancer.Trends in cell biology · 2023Review
- Tumour Genetic Heterogeneity in Relation to Oral Squamous Cell Carcinoma and Anti-Cancer Treatment.International journal of environmental research and public health · 2023Review
- DeepSom: a CNN-based approach to somatic variant calling in WGS samples without a matched normal.Bioinformatics (Oxford, England) · 2023Article
25 more citing papers are in PubMed but not listed here.
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3 authors.
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Abstract
Cancer progression is an example of a rapid adaptive process where evolving new traits is essential for survival and requires a high mutation rate. Precancerous cells acquire a few key mutations that drive rapid population growth and carcinogenesis. Cancer genomics demonstrates that these few driver mutations occur alongside thousands of random passenger mutations--a natural consequence of cancer's elevated mutation rate. Some passengers are deleterious to cancer cells, yet have been largely ignored in cancer research. In population genetics, however, the accumulation of mildly deleterious mutations has been shown to cause population meltdown. Here we develop a stochastic population model where beneficial drivers engage in a tug-of-war with frequent mildly deleterious passengers. These passengers present a barrier to cancer progression describable by a critical population size, below which most lesions fail to progress, and a critical mutation rate, above which cancers melt down. We find support for this model in cancer age-incidence and cancer genomics data that also allow us to estimate the fitness advantage of drivers and fitness costs of passengers. We identify two regimes of adaptive evolutionary dynamics and use these regimes to understand successes and failures of different treatment strategies. A tumor's load of deleterious passengers can explain previously paradoxical treatment outcomes and suggest that it could potentially serve as a biomarker of response to mutagenic therapies. The collective deleterious effect of passengers is currently an unexploited therapeutic target. We discuss how their effects might be exacerbated by current and future therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.