Targeted therapeutic options and future perspectives for HER2-positive breast cancer

Abstract

Over the past 2 decades, there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) are commonly recommended anti-HER2 target agents by the U.S. Food and Drug Administration. This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices. In this article, we present the data on anti-HER2 clinical research of neoadjuvant, adjuvant, and metastatic studies from the past 2 decades. We also highlight some of the promising strategies that should be critically considered. Lastly, this review lists some of the ongoing clinical trials, findings of which may soon be available.

Keywords: Breast cancer; Drug development.

Fig. 1

Schematic representation of human epidermal growth factor (Erb) family and ligands. Formation of different homo- and heterodimers were induced by specific ligand, triggering the recruitment of various downstream adapters, resulting in the activation of numerous signal transduction pathways. HER2/neu has no known ligands and that HER3 has no intrinsic tyrosine kinase activity

Fig. 2

Trastuzumab and pertuzumab bind to different regions on HER2. Trastuzumab suppresses HER2 activity but does not inhibit heterodimerization. Pertuzumab has the capability of binding to the extracellular dimerization subdomain of the HER2 receptor, reducing HER2 intracellular signaling events by blocking heterodimerization with other HER receptors

Fig. 3

Mechanism of lapatinib action. By competing with ATP, small-molecule TKI Lapatinib blocks HER2 signaling, preventing auto phosphorylation and subsequent downstream signaling events