An overview of resistance to Human epidermal growth factor receptor 2 (Her2) targeted therapies in breast cancer

Ahmed M Elshazly; David A Gewirtz

doi:10.20517/cdr.2022.09

An overview of resistance to Human epidermal growth factor receptor 2 (Her2) targeted therapies in breast cancer

Cancer Drug Resist. 2022 Jun 1;5(2):472-486. doi: 10.20517/cdr.2022.09. eCollection 2022.

Authors

Ahmed M Elshazly^{1

2}, David A Gewirtz²

Affiliations

¹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
² Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.

Abstract

Breast cancer (BC) is the second most common cause of cancer-related deaths and the most frequently diagnosed cancer in females. Among breast cancer types, HER2-positive breast cancer occurs in nearly 20% of human breast cancers and is associated with increased aggressiveness, poor prognosis, and shortened overall survival. HER2+ breast cancer is currently managed with multidisciplinary treatment strategies including surgery, radiation, chemotherapy, and targeted therapy. Drug resistance remains a continuing challenge, especially to targeted therapy utilizing monoclonal antibodies and tyrosine kinase inhibitors. This review discusses some of the recent molecular mechanisms that are involved in the development of resistance to Her2-targeted therapies including the PI3K/Akt/mTOR pathway, IGF-IR, Src, c-MET, the PP2A family, CD36, p27^kip1 _, and miRNAs.

Keywords: CD36; HER2+; IGF-IR; PP2A; Src; Targeted therapy resistance; c-MET; miRNA.

Publication types

Review