Sunday 24 March 2013
KRAS gene amplification
- 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.
- The emergence of KRAS mutations but also KRAS amplification is associated with acquired resistance to the EGFR inhibitors cetuximab or panitumumab.
- KRAS amplification may also be responsible for primary resistance to these agents.
- KRAS amplification is detected in 0.67% of CRC specimens. KRAS amplification is 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.
KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Valtorta E, Misale S, Sartore-Bianchi A, Nagtegaal ID, 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 CJ, Gambacorta M, Bardelli A, Di Nicolantonio F. Int J Cancer. 2013 Feb 12. doi : 10.1002/ijc.28106 PMID: 23404247