ArticleMolecular oncology2019
RAS and BRAF mutations in cell-free DNA are predictive for outcome of cetuximab monotherapy in patients with tissue-tested RAS wild-type advanced colorectal cancer.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Circulating tumour DNA and its clinical utility in predicting treatment response or survival in patients with metastatic colorectal cancer: a systematic review and meta-analysis.British journal of cancer · 2022Pooled it
- Monitoring levels of circulating cell-free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment.Molecular oncology · 2021Trial
- MiR-31 as a predictive biomarker of cetuximab efficacy in metastatic colorectal cancer patients: systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Review
- Effect of sex differences on the emergence of ctDNA RAS mutations in RAS wild-type colorectal cancer.Scientific reports · 2026Article
- Research trends and prospects of Circulating tumor DNA associated with colorectal cancer: a bibliometric analysis.Discover oncology · 2025Article
- Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions.International journal of molecular sciences · 2025Review
- Colorectal Cancer: Genetic Underpinning and Molecular Therapeutics for Precision Medicine.Genes · 2024Review
- Detection of circulatory E. granulosus-derived cell-free DNA in the plasma and urine of human cystic echinococcosis using an in-house PCR: a potential promising diagnostic biomarker.Molecular biology reports · 2024Article
- Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival.International journal of molecular sciences · 2023Article
- Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers.Cancer research and treatment · 2023Article
- Differential presence of exons (DPE): sequencing liquid biopsy by NGS. A new method for clustering colorectal Cancer patients.BMC cancer · 2023Article
- Review
- Co-delivery systems: hope for clinical application?Drug delivery and translational research · 2022Review
- Genome-wide aneuploidy detected by mFast-SeqS in circulating cell-free DNA is associated with poor response to pembrolizumab in patients with advanced urothelial cancer.Molecular oncology · 2022Article
- Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Overview of serum and tissue markers in colorectal cancer: a primer for radiologists.Abdominal radiology (New York) · 2021Review
- High-throughput and affordable genome-wide methylation profiling of circulating cell-free DNA by methylated DNA sequencing (MeD-seq) of LpnPI digested fragments.Clinical epigenetics · 2021Article
- Review
- Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA.NPJ precision oncology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In metastatic colorectal cancer, RAS and BRAF mutations cause resistance to anti-EGFR therapies, such as cetuximab. Heterogeneity in RAS and BRAF mutations might explain nonresponse in a subset of patients receiving cetuximab. Analyzing mutations in plasma-derived circulating tumor DNA (ctDNA) could provide a more comprehensive overview of the mutational landscape as compared to analyses of primary and/or metastatic tumor tissue. Therefore, this prospective multicenter study followed 34 patients with metastatic colorectal cancer who were tissue-tested as RAS wild-type (exons 2-4) during routine work-up and received third-line cetuximab monotherapy. BRAF mutation status was also tested but did not exclude patients from therapy. At baseline and upon disease progression, cell-free DNA (cfDNA) was isolated for targeted next-generation sequencing (NGS). At 8 weeks, we determined that patients had benefited from treatment. NGS of cfDNA identified three patients with RAS mutations not detected in tumor tissue during routine work-up. Another six patients had a BRAF or rare RAS mutation in ctDNA and/or tumor tissue. Relative to patients without mutations in RAS/BRAF, patients with mutations at baseline had shorter progression-free survival [1.8 versus 4.9 months (P < 0.001)] and overall survival [3.1 versus 9.4 months (P = 0.001)]. In patients with clinical benefit (progressive disease after 8 weeks), ctDNA testing revealed previously undetected mutations in RAS/BRAF (71%) and EGFR (47%), which often emerged polyclonally. Our results indicate that baseline NGS of ctDNA can identify additional RAS mutation carriers, which could improve patient selection for anti-EGFR therapies. Acquired resistance, in patients with initial treatment benefit, is mainly explained by polyclonal emergence of RAS, BRAF, and EGFR mutations in ctDNA.
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