Trastuzumab (Anti-HER2 Antibody)

Trastuzumab is a humanized IgG1 recombinantmonoclonal antibody that selectively binds to HER2 (eceptor tyrosine-protein kinase ErbB-2) with high affinity. Trastuzumab can be used for the research of HER2-positive metastatic breast and gastric cancer. Trastuzumab consists of two antigen-specific sites that bind to the juxtamembrane portion of the extracellular domain of the HER2 receptor and that prevent the activation of its intracellular tyrosine kinase. Trastuzumab recruits immune effector cells that are responsible for antibody-dependent cytotoxicity. HER2 (human epidermal growth factor receptor 2), also known as erbB-2 or CD340, is a tyrosine kinase receptor of the EFGR family of proteins. There is no known ligand, but it can form homodimers or heterodimers with other HER proteins. Once active, it activates the MAPK (mitogen-activated protein kinase) and PI3K (phosphatidylinositol-3 kinase) signaling pathways resulting in cell cycle progression and cell proliferation. HER2 over-expression is also known to occur in breast, ovarian, stomach, lung adenocarcinoma, aggressive forms of uterine cancer and gastric cancer. In 1990 the FDA approved the use of the monoclonal antibody trastuzumab in breast and stomach cancer. Other strategies to target HER2 that have been approved include ADCs (antibody-drug conjugate) and margetuximab (an anti-HER2 antibody that can alter the Fc-receptor affinity to CD16 and induce cytotoxicity). The use of small molecule tyrosine kinase inhibitors, alone or in combinatory therapy, has shown great promise in the treatment of HER2+ breast cancer (BC). However, resistance to treatment, for instance by mutations on HER2 or upregulation of other HER receptors, has been described. Neratinib, a pan-HER2 inhibitor, was approved in 2017 for early-stage BC, as adjuvant anti-HER2 therapy after trastuzumab treatment. However, side effects limit its use. The development of treatments targeting early-stage cancer, with minimal side effects and resistance development, will bring major benefits to HER2+ oncology patients.