Monoclonal Antibodies, Small Molecule Inhibitors and Antibody-drug Conjugates as HER2 Inhibitors

The human epidermal growth factor receptor family, including HER1/EGFR/ErbB1, HER2/NEU/ErbB2, HER3/ErbB3 and HER4/ErbB4, belongs to transmembrane receptor tyrosine kinases (RTKs) and participates in signal transduction and oncogenesis [1, 2]. These epidermal growth factor receptors have similar structures, including an extracellular domain (ECD), a transmembrane domain, and an intracellular tyrosine kinase domain [3]. The extracellular domain, containing domains I, II, III, and IV, is related to ligands binding and homo and heterodimer formation, while the intracellular domain, containing phosphorylation sites, ABSTRACT Overexpression of human epidermal growth factor receptor (HER)-2 is found in a variety of cancers, often portending poor clinical outcomes. Therefore, HER2 is an attractive target for treatment. This review describes the research progress of HER2 targeted inhibitors in recent years. Excellent reviews are available, so we focus on the development, mechanisms of action, and structure-activity relationships of different types of inhibitors, including monoclonal antibodies, small molecule inhibitors, and antibody-drug conjugates (ADCs). In addition, the differences among them are compared.

Automated summary

The human epidermal growth factor receptor family, including HER1/EGFR/ErbB1, HER2/NEU/ErbB2, HER3/ErbB3 and HER4/ErbB4, belongs to transmembrane receptor tyrosine kinases (RTKs) and participates in signal transduction and oncogenesis. These receptors have similar structures, with extracellular and intracellular domains serving different functions.