ArticleScientific reports2019
Genomic characterization of intrinsic and acquired resistance to cetuximab in colorectal cancer patients.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 78 citations in OpenAlex.
- Amivantamab Monotherapy in ChemorefractoryJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Acquired Genomic Alterations on First-Line Chemotherapy With Cetuximab in Advanced Colorectal Cancer: Circulating Tumor DNA Analysis of the CALGB/SWOG-80405 Trial (Alliance).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Trial
- Two Worlds, One Battle: How Bacteria and Malignancies Converge on Drug Resistance.International journal of molecular sciences · 2026Review
- EGFR Signaling in Colorectal Cancer: Novel Therapeutic Strategies, Predictive Biomarkers, and Counteracting Treatment Resistance.International journal of molecular sciences · 2026Review
- Harnessing transcriptomics for discovery of natural products to overcome acquired cancer resistance.Archives of pharmacal research · 2026Review
- From PIK3CA Mutations to Rational PI3K Inhibition for the Treatment of Colorectal Cancer.Molecular diagnosis & therapy · 2026Review
- Anti-EGFR Therapy in Metastatic Colorectal Cancer: Identifying, Tracking, and Overcoming Resistance.Cancers · 2025Review
- Targeted siRNA Delivery Using Cetuximab-Conjugated Starch for Epidermal Growth Factor Receptor-Driven Head and Neck Squamous Cell Carcinoma.Small science · 2025Article
- Review
- Is the transverse colon the new right?-similarities in EGFR drug response and prognosis.Journal of gastrointestinal oncology · 2024Article
- Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- A panorama of colon cancer in the era of liquid biopsy.The journal of liquid biopsy · 2024Review
- Drug Resistance and Novel Targets for Cancer Therapy: An Overview of Recent Findings.Biomedicines · 2024Article
- Circulating Tumor DNA Enables Sensitive Detection of Actionable Gene Fusions and Rearrangements Across Cancer Types.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Unveiling acquired resistance to anti-EGFR therapies in colorectal cancer: a long and winding road.Frontiers in pharmacology · 2024Review
- Characterization of Expression-Based Gene Clusters Gives Insights into Variation in Patient Response to Cancer Therapies.Cancer informatics · 2024Article
- Single-cell and spatial transcriptome analysis reveals the cellular heterogeneity of liver metastatic colorectal cancer.Science advances · 2023Article
- Histological transformation to signet-ring cell carcinoma in a patient with clinically aggressive poorly differentiated adenocarcinoma of the ascending colon after response to chemotherapy plus cetuximab: a case report.World journal of surgical oncology · 2023Article
- Circulating Tumor DNA Identifies Diverse Landscape of Acquired Resistance to Anti-Epidermal Growth Factor Receptor Therapy in Metastatic Colorectal Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-EGFR antibodies are effective in therapies for late-stage colorectal cancer (CRC); however, many tumours are unresponsive or develop resistance. We performed genomic analysis of intrinsic and acquired resistance to anti-EGFR therapy in prospectively collected tumour samples from 25 CRC patients receiving cetuximab (an EGFR inhibitor). Of 25 CRC patients, 13 displayed intrinsic resistance to cetuximab; 12 were intrinsically sensitive. We obtained six re-biopsy samples at acquired resistance from the intrinsically sensitive patients. NCOA4-RET and LMNA-NTRK1 fusions and NRG1 and GNAS amplifications were found in intrinsic-resistant patients. In cetuximab-sensitive patients, we found KRAS K117N and A146T mutations in addition to BRAF V600E, AKT1 E17K, PIK3CA E542K, and FGFR1 or ERBB2 amplifications. The comparison between baseline and acquired-resistant tumours revealed an extreme shift in variant allele frequency of somatic variants, suggesting that cetuximab exposure dramatically selected for rare resistant subclones that were initially undetectable. There was also an increase in epithelial-to-mesenchymal transition at acquired resistance, with a reduction in the immune infiltrate. Furthermore, characterization of an acquired-resistant, patient-derived cell line showed that PI3K/mTOR inhibition could rescue cetuximab resistance. Thus, we uncovered novel genomic alterations that elucidate the mechanisms of sensitivity and resistance to anti-EGFR therapy in metastatic CRC patients.
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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.