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Review
. 2020 Jun:86:102023.
doi: 10.1016/j.ctrv.2020.102023. Epub 2020 Apr 13.

Resistance to anti-epidermal growth factor receptor in metastatic colorectal cancer: What does still need to be addressed?

Giulia Martini  1 , Davide Ciardiello  1 , Pietro Paolo Vitiello  1 , Stefania Napolitano  1 , Claudia Cardone  1 , Antonio Cuomo  2 , Teresa Troiani  1 , Fortunato Ciardiello  1 , Erika Martinelli  1
Affiliations
Review

Resistance to anti-epidermal growth factor receptor in metastatic colorectal cancer: What does still need to be addressed?

Giulia Martini et al. Cancer Treat Rev. 2020 Jun.

Abstract

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.

Keywords: Biomarkers; Colorectal cancer; Epidermal growth factor receptor; Mechanism of resistance; Molecular alterations; Monoclonal antibodies; Mutant allele fraction.

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Conflict of interest statement

Declaration of Competing Interest Davide Ciardiello: Travel Grant from Sanofi Teresa Troiani: Amgen, Bayer, Merck KgA, Roche, Sanofi. Fortunato Ciardiello: Advisory Board role for Amgen, Roche, Merck KgA, Servier, Bayer, Array. Institutional research funding from: Amgen, Roche, Merck KgA, Servier, Bayer, Array, Ipsen, MSD, BMS, Symphogen. Erika Martinelli: Advisory Board role for Amgen, Astra-Zeneca, Bayer, Merck KgA, Roche, Servier, Sanofi. All other authors have no conflicts of interest to declare.

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