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World J Clin Cases. Oct 6, 2018; 6(11): 418-425
Published online Oct 6, 2018. doi: 10.12998/wjcc.v6.i11.418
Dual HER2 inhibition strategies in the management of treatment-refractory metastatic colorectal cancer: History and status
Ozkan Kanat, Hulya Ertas, Burcu Caner
Ozkan Kanat, Hulya Ertas, Burcu Caner, Department of Medical Oncology, Faculty of Medicine, Uludag University, Bursa 16059, Turkey
Author contributions: Kanat O assigned the issue, collected relevant literature data, and wrote the manuscript; Ertas H and Caner B performed literature research and contributed to the final version of the manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ozkan Kanat, MD, PhD, Professor, Department of Medical Oncology, Faculty of Medicine, Uludag University, Gorukle, Bursa 16059, Turkey. ozkanat@uludag.edu.tr
Telephone: +90-224-2951321 Fax: +90-224-2951341
Received: April 10, 2018
Peer-review started: April 10, 2018
First decision: April 27, 2018
Revised: May 15, 2018
Accepted: June 8, 2018
Article in press: June 8, 2018
Published online: October 6, 2018
Abstract

Human epidermal growth factor receptor 2 (HER2) signaling pathway activation has been identified as a contributor to de novo or acquired resistance to epidermal growth factor receptor (EGFR) inhibitors in a small subset of patients with metastatic colorectal cancer (mCRC). Dual anti-HER2-targeted treatment exhibits strong antitumor activity in preclinical models of HER2-positive mCRC, supporting its testing in clinical trials. The HERACLES trial at four Italian academic cancer centers has confirmed the effectiveness of dual blockage of HER2 with trastuzumab plus lapatinib in patients with heavily pretreated HER2-positive mCRC, refractory to the anti-EGFR antibodies cetuximab or panitumumab. Here, we reviewed the preclinical studies exploring the role of HER2 signaling in the development of anti-EGFR therapy resistance and discussed the status of clinical trials assessing the activity of HER2 inhibitors in this setting.

Keywords: Epidermal growth factor receptor, Cetuximab, Panitumumab, Human epidermal growth factor receptor 2, Anti-epidermal growth factor receptor resistance, Trastuzumab, Dual inhibition

Core tip: We reviewed the preclinical studies exploring the role of human epidermal growth factor receptor 2 (HER2) signaling in the development of anti-epidermal growth factor receptor therapy resistance in metastatic colorectal cancer and discussed the status of clinical trials assessing the activity of HER2 inhibitors in this setting.