Oncogenic mutations as predictive factors in colorectal cancer

Lièvre, A; Blons, H; Laurent-Puig, P

doi:10.1038/onc.2010.89

Cited by 117Colorectal Cancer Treatments and StudiesLung Cancer Treatments and MutationsGenetic factors in colorectal cancer

Oncogenic mutations as predictive factors in colorectal cancer

Lièvre, A, Blons, H, Laurent-Puig, P·2010·Oncogene

DOI 10.1038/onc.2010.89

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Abstract

The anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies cetuximab and panitumumab have been demonstrated to be new therapeutic options for metastatic colorectal cancer (mCRC). Oncogenic activation of intracellular signalling pathways downstream of EGFR has a major role in colorectal carcinogenesis but has also been reported to be an important mechanism of resistance to anti-EGFR antibodies. Among the activating mutations found in colorectal cancers, tumour KRAS mutations, which are found in approximately 40% of the cases, have been widely demonstrated as a major predictive marker of resistance to cetuximab or panitumumab, therefore, opening the way to individualized treatment for patients with mCRC. Other oncogenic mutations, such as BRAF or PIK3CA mutations or loss of PTEN expression, may also be additional interesting predictive markers of response to anti-EGFR monoclonal antibodies but required further evaluation before being incorporated in clinical practice. The identification of these molecular markers involved in the resistance of anti-EGFR antibodies will allow the development of new therapies that should target 'escape mechanisms' used by tumours to circumvent a pathway that has been pharmacologically blocked by anti-EGFR.

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KRAS exon 2 mutations are major determinants of primary resistance to cetuximab or panitumumab.
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From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [27]

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Authors: Lièvre, A., Blons, H., & Laurent-Puig, P.
Affiliations: Inserm (FR)
ORCID: Lièvre, A
Blons, H
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2010-04-12
Volume: 29
Issue: 21
Pages: 3033-3043
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/onc.2010.89
OpenAlex: W2004934664
Cited by: 117
References: 102
Citations by year: 2026: 3 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 2 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 21 · 2012: 17
FWCI: 1.97
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: colorectal cancer, metastatic colorectal cancer, anti-EGFR monoclonal antibody, cetuximab, panitumumab, KRAS mutation, predictive biomarkers, drug resistance, BRAF mutation, PIK3CA mutation, PTEN loss, personalized treatment
MeSH terms: Cetuximab, Panitumumab, Antibodies, Monoclonal, Humans, Mutation, Oncogenes, Predictive Value of Tests, Colorectal Neoplasms, Randomized Controlled Trials as Topic, Treatment Outcome, Phosphatidylinositol 3-Kinases, Antibodies, Monoclonal, Humanized, ErbB Receptors

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Oncogenic mutations as predictive factors in colorectal cancer

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