ArticleCancer research2017
The Damaging Effect of Passenger Mutations on Cancer Progression.
Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed.
- Tumor cell intrinsic mechanisms of immune escape.Cell communication and signaling : CCS · 2026Review
- The nuclease EXO1 promotes genomic instability by degrading nascent DNA in BRCA-proficient cells.Nature communications · 2026Article
- Interpreting cancer genetics through a two-step "evolutionary cascade hypothesis": bridging neutral and selective perspectives.Journal of translational medicine · 2026Review
- Effect of chemotherapy on passenger mutations in metastatic colorectal cancer.Molecular oncology · 2026Article
- Gene amplification in the premalignant stages of non-small cell lung cancer development.Frontiers in oncology · 2026Review
- Cancer-associated loss-of-function mutations in KCNQ1 enhance Wnt/β-catenin signalling disrupting epithelial homeostasis.Oncogene · 2025Article
- Epigenetics of Endometrial Cancer: The Role of Chromatin Modifications and Medicolegal Implications.International journal of molecular sciences · 2025Review
- Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations.International journal of molecular sciences · 2025Article
- Genetic Ancestry and Lung Cancer in Latin American Patients: A Crucial Step for Understanding a Diverse Population.Clinical lung cancer · 2025Review
- Oncometabolites at the crossroads of genetic, epigenetic and ecological alterations in cancer.Cell death and differentiation · 2024Review
- Article
- Machine learning optimized DriverDetect software for high precision prediction of deleterious mutations in human cancers.Scientific reports · 2024Article
- The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities.Current oncology (Toronto, Ont.) · 2024Review
- Strength of selection in lung tumors correlates with clinical features better than tumor mutation burden.Scientific reports · 2024Article
- Synergistic epistasis among cancer drivers can rescue early tumors from the accumulation of deleterious passengers.PLoS computational biology · 2024Article
- Review
- Special Issue "From Basic Science to Treatment Strategies: Personalized Cancer Therapy".International journal of molecular sciences · 2024Article
- Reuniting philosophy and science to advance cancer research.Biological reviews of the Cambridge Philosophical Society · 2023Article
- Cancer genomes tolerate deleterious coding mutations through somatic copy number amplifications of wild-type regions.Nature communications · 2023Article
- 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
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Genomic instability and high mutation rates cause cancer to acquire numerous mutations and chromosomal alterations during its somatic evolution; most are termed passengers because they do not confer cancer phenotypes. Evolutionary simulations and cancer genomic studies suggest that mildly deleterious passengers accumulate and can collectively slow cancer progression. Clinical data also suggest an association between passenger load and response to therapeutics, yet no causal link between the effects of passengers and cancer progression has been established. To assess this, we introduced increasing passenger loads into human cell lines and immunocompromised mouse models. We found that passengers dramatically reduced proliferative fitness (∼3% per Mb), slowed tumor growth, and reduced metastatic progression. We developed new genomic measures of damaging passenger load that can accurately predict the fitness costs of passengers in cell lines and in human breast cancers. We conclude that genomic instability and an elevated load of DNA alterations in cancer is a double-edged sword: it accelerates the accumulation of adaptive drivers, but incurs a harmful passenger load that can outweigh driver benefit. The effects of passenger alterations on cancer fitness were unrelated to enhanced immunity, as our tests were performed either in cell culture or in immunocompromised animals. Our findings refute traditional paradigms of passengers as neutral events, suggesting that passenger load reduces the fitness of cancer cells and slows or prevents progression of both primary and metastatic disease. The antitumor effects of chemotherapies can in part be due to the induction of genomic instability and increased passenger load.
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Registered trials
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.