Journal
CANCER TREATMENT REVIEWS
Volume 36, Issue -, Pages S1-S5Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S0305-7372(10)70012-8
Keywords
Colorectal cancer; KRAS; EGFR; Monoclonal antibodies
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Funding
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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Metastatic colorectal cancer (mCRC) patients carrying KRAS mutated tumors do not benefit from epidermal growth factor receptor (EGFR)-targeted cetuximab- or panitumumab-based therapies. Indeed, the mutational status of KRAS is currently a validated predictive biomarker employed to select mCRC patients for EGFR targeted drugs. When patients fail standard 5-fluorouracil-, oxaliplatin-, irinotecan- and bevacizumab-based therapies, EGFR-targeted salvage therapy can be prescribed only for those individuals with KRAS wild-type cancer. Thus, clinicians are now facing the urgent issue of better understanding the biology of KRAS mutant disease, in order to devise novel effective therapies in such defined genetic setting. In addition to KRAS, recent data point out that BRAF and PIK3CA exon 20 mutations hamper response to EGFR-targeted treatment in mCRC, potentially excluding from treatment also patients with these molecular alterations in their tumor. This review will focus on current knowledge regarding the molecular landscape of mCRC including and beyond KRAS, and will summarize novel rationally-developed combinatorial regimens that are being evaluated in early clinical trials. (C) 2010 Elsevier Ltd. All rights reserved.
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