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Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Beyond RAS: The Role of Epidermal Growth Factor Receptor (EGFR) and its Network in the Prediction of Clinical Outcome During Anti-EGFR Treatment in Colorectal Cancer Patients

Author(s): Riccardo Giampieri, Giuseppe Aprile, Michela Del Prete, Luca Faloppi, Maristella Bianconi, Marta Bonotto, Giampiero Fasola, Stefano Cascinu and Mario Scartozzi

Volume 15 , Issue 13 , 2014

Page: [1225 - 1230] Pages: 6

DOI: 10.2174/1389450115666141109212801

Price: $65

Abstract

Although the extended RAS analysis allows a better identification of patients potentially candidates to anti- EGFR monoclonal antibodies, a significant proportion of tumours may still reveals refractory to such a treatment approach. In these latter cases patients are then exposed to unnecessary toxicities without clinical benefit. Among many further biological factors that may have a role in determining resistance/sensitivity to EGFR-inhibitors, the EGFR itself, other members of the HER family (i.e. HER-2 and HER-3) as well as other surface receptors such as the IGF-1 receptor seem of particular interest. Preclinical models have shown that these receptors are biologically connected to each other and able to directly or indirectly influence the downstream molecular pathways. In the presence of abnormal expression of these biological determinants, intracellular pathways may become independent from the receptor-targeting treatment thus making therapies directed against the receptor ineffective. Clinical observations and translational studies seem to confirm these findings. The Authors have reviewed the literature and have selected recent clinical reports focusing on translational research on the EGFR itself or on other molecules that may interfere with this pathway. We also discuss potential future developments in this area.

Keywords: Cetuximab, cMET, colorectal cancer, EGFR, HER-3, IGF1-R, panitumumab.

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