ArticleNature ecology & evolution2021
Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer.
Article in Nature ecology & evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Clinical Validity of FoundationOne Liquid CDx for Detection of BRAFV600E in Colorectal Cancer.Cancer research communications · 2025Trial
- Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.Nature medicine · 2024Trial
- Cancer evolution and multi-omic profile of relapsed colorectal liver metastases after treatment.Genome medicine · 2026Article
- Integrating liquid biopsy and mutational signatures to advance precision oncology.NPJ precision oncology · 2026Review
- Detection of heterogeneous resistance mechanisms to tyrosine kinase inhibitors from cell-free DNA.Cell genomics · 2025Article
- Impact of treatment history on drug resistance of metastatic colorectal cancer organoids.iScience · 2025Article
- Survival outcome prediction of esophageal squamous cell carcinoma patients based on radiomics and mutation signature.Cancer imaging : the official publication of the International Cancer Imaging Society · 2025Article
- Comprehensive molecular characterization of early stage grade 3 endometrioid endometrial adenocarcinoma.Gynecologic oncology · 2024Article
- Mutational Signatures in Colorectal Cancer: Translational Insights, Clinical Applications, and Limitations.Cancers · 2024Review
- Review
- Mutational signatures of colorectal cancers according to distinct computational workflows.Briefings in bioinformatics · 2024Article
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Phenotypic switching as a non-genetic mechanism of resistance predicts antibody therapy regimens.iScience · 2024Article
- Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.Nature genetics · 2024Article
- Analysis of translesion polymerases in colorectal cancer cells following cetuximab treatment: A network perspective.Cancer medicine · 2024Article
- Circulating Tumor DNA to Drive Treatment in Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Reshaping the Pancreatic Cancer Microenvironment at Different Stages with Chemotherapy.Cancers · 2023Review
- Resistance Mechanisms to Anti-Epidermal Growth Factor Receptor Therapy inJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Molecular screening with liquid biopsy for anti-EGFR retreatment in metastatic colorectal cancer: preliminary data from the randomized phase 2 PARERE trial.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRCs), but acquired resistance invariably evolves. It is unknown which mutational mechanisms enable resistance evolution and whether adaptive mutagenesis (a transient cetuximab-induced increase in mutation generation) contributes in patients. Here, we investigate these questions in exome sequencing data from 42 baseline and progression biopsies from cetuximab-treated CRCs. Mutation loads did not increase from baseline to progression, and evidence for a contribution of adaptive mutagenesis was limited. However, the chemotherapy-induced mutational signature SBS17b was the main contributor of specific KRAS/NRAS and EGFR driver mutations that are enriched at acquired resistance. Detectable SBS17b activity before treatment predicted shorter progression-free survival and the evolution of these specific mutations during subsequent cetuximab treatment. This result suggests that chemotherapy mutagenesis can accelerate resistance evolution. Mutational signatures may be a new class of cancer evolution predictor.
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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.