KRAS gene amplification in colorectal cancer and impact on response to EGFR‐targeted therapy
Open accessAbstract
KRAS mutations are the most common oncogenic event in colorectal cancer (CRC) progression and their occurrence is associated with lack of response to anti epidermal growth factor receptor (EGFR) targeted therapies. Using preclinical models and patients' samples we recently reported that the emergence of KRAS mutations but also KRAS amplification is associated with acquired resistance to the EGFR inhibitors cetuximab or panitumumab. We reasoned that KRAS amplification may also be responsible for primary resistance to these agents. Furthermore, while the prevalence of KRAS mutations has been well established in CRC, little is known about the frequency of KRAS amplification in large CRC series. We performed a screening of 1,039 CRC samples to assess the prevalence of KRAS amplification in this tumor type and further evaluated the role of this genetic alteration on the sensitivity to anti EGFR therapies. We detected KRAS amplification in 7/1,039 (0.67%) and 1/102 evaluable CRC specimens and cell lines, respectively. KRAS amplification was mutually exclusive with KRAS mutations. Tumors or cell lines harboring this genetic lesion are not responsive to anti‐EGFR inhibitors. Although KRAS amplification is an infrequent event in CRC, it might be responsible for precluding response to anti‐EGFR treatment in a small proportion of patients.
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KRAS amplification occurs at a very low frequency (0.7%) and correlates with primary resistance.
“A very low frequency of KRAS amplification (0.7 %) has also been reported and found to correlate with primary resistance [36].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [36]
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- Authors
- Valtorta, E., Misale, S., Sartore‐Bianchi, A., Nagtegaal, I. D., Paraf, F., Lauricella, C., Dimartino, V., Hobor, S., Jacobs, B., Ercolani, C., Lamba, S., Scala, E., Veronese, S., Laurent‐Puig, P., Siena, S., Tejpar, S., Mottolese, M., Punt, C. J. A., Gambacorta, M., Bardelli, A., & Di Nicolantonio, F.
- Affiliations
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Candiolo Cancer Institute (IT)
- The Falck Division of Medical Oncology Ospedale Niguarda Ca' Granda Piazza Ospedale Maggiore 3 Milano Italy
- Department of Pathology Radboud University Nijmegen Medical Centre Nijmegen The Netherlands
- Hôpital Universitaire Dupuytren (FR)
- Instituto Nazionale Tumori Regina Elena (IT)
- University of Turin (IT)
- KU Leuven (BE)
- Inserm (FR)
- Amsterdam UMC Location University of Amsterdam (NL)
- IFOM (IT)
- Department of Oncology University of Torino Candiolo (Torino) Italy
- ORCID
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2013-03-16
- Volume
- 133
- Issue
- 5
- Pages
- 1259-1265
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2150840254
- Cited by
- 175
- References
- 26
- Citations by year
- 2026: 2 · 2024: 9 · 2023: 2 · 2022: 13 · 2021: 16 · 2020: 16 · 2019: 19 · 2018: 18 · 2017: 11 · 2016: 22 · 2015: 16 · 2014: 25 · 2013: 6
- FWCI
- 12.31
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Amgen
- European Commission (259015)
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro (12812, 5 x mille)
- Regione Piemonte
- Vlaamse regering
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- KRAS amplification, colorectal cancer, anti-EGFR therapy, cetuximab, panitumumab, KRAS mutation, primary resistance
- MeSH terms
- Gene Amplification, Humans, Proto-Oncogene Proteins, Retrospective Studies, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras), ras Proteins, Cell Line, Tumor, ErbB Receptors
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