HER 2 Targeted Therapy and Its Potential Risk of Drug Resistance

Abstract

HER2, human epidermal receptor 2(c-erbB-2 gene), is a hot targeted point in various cancers targeted therapy. Breast cancer including HER2 positive or negative. HER2 is an oncogenic receptor tyrosine kinase. HER2 gene amplification occurs in some of breast cancers (BCS), resulting in overexpression of the HER2 protein. Compared to the trastuzumab or pertuzumab, the performance of trastuzumab deruxtecan is excellent. Drug resistance is known to be the main cause of failure of tumor chemotherapy. Tumor drug resistance involves various mechanisms, such as those involving decreased intracellular drug concentration, changes of drug target molecules, metabolic detoxification, and imbalance of DNA damage repair function. HER2-positive breast cancer becomes resistant to trastuzumab, thereby blocking effective binding and developing resistance. The significance of this review is to understand the mechanism of drug resistance from molecular and chemotherapy perspectives by studying the structure and overexpression of HER2 protein as predictors, so as to grasp the progress of current targeted drug therapy. Our review starting from HER2 and its targeted therapy gets to the deep insight into the antibody drug conjugates and explores the possible proteins which may become the potential targeted points in future research.