Targeting HER2 expression in cancer: New drugs and new indications

Semir Vranić; Semir Bešlija; Zoran Gatalica

doi:10.17305/bjbms.2020.4908

Authors

Semir Vranić College of Medicine, QU Health, Qatar University, Doha, Qatar https://orcid.org/0000-0001-9743-7265
Semir Bešlija Department of Oncology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0002-3066-3871
Zoran Gatalica Creighton University School of Medicine, Phoenix, Arizona, United States and Oklahoma University College of Medicine, Oklahoma City, Oklahoma, United States

DOI:

https://doi.org/10.17305/bjbms.2020.4908

Keywords:

HER2, targeted therapy, mutations, amplification

Abstract

Functional activation of human epidermal growth factor receptor 2 (HER2) has been shown to strongly promote carcinogenesis, leading to the investigation of HER2-directed agents in cancers with HER2 genomic alterations. This has been best documented in the context of HER2 gene amplification in breast and gastric/gastroesophageal junction carcinomas for which several HER2-directed agents are available and have become a part of standard treatment regimens. Somatic HER2 gene mutations have been recently described at low frequency in a variety of human cancers and have emerged as a novel predictive biomarker for HER2-directed therapies. Preclinical data also indicate that activating HER2 mutations are potent oncogenic drivers in a manner that is analogous to HER2 amplification. HER2 mutations may clinically confer sensitivity to HER2-directed agents as recently shown in a phase II clinical trial with antibody-drug conjugate against HER2 trastuzumab deruxtecan in patients with non-squamous non-small cell lung carcinoma.