Journal
CANCER TREATMENT REVIEWS
Volume 86, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ctrv.2020.102023
Keywords
Colorectal cancer; Epidermal growth factor receptor; Monoclonal antibodies; Mechanism of resistance; Biomarkers; Molecular alterations; Mutant allele fraction
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Funding
- Regione Campania Cancer Research Campaign I-Cure Grant
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Colorectal cancer (CRC) represents a global health problem, being one of the most diagnosed and aggressive tumors. Cetuximab and panitumumab monoclonal antibodies (mAbs) in combination with chemotherapy are an effective strategy for patients with RAS Wild Type (WT) metastatic colorectal cancer (mCRC). However, tumors are often unresponsive or develop resistance. In the last years, molecular alterations in principal oncogenes (RAS, BRAF, PI3KCA, PTEN) in the downstream pathway of the epidermal growth factor receptor (EGFR) and in other receptors (HER2, MET) that converge on MAPK-ERK signalling have been identified as novel mechanisms of resistance to anti-EGFR strategies. However, further efforts are needed to better stratify CRCs and ensure more individualized treatments. Herein, we describe the consolidated molecular drivers of resistance and the therapeutic strategies available so far, with an overview on potential biomarkers of response that could be integrated in clinical practice.
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