Current and emerging therapies of HER2-positive metastatic breast cancer

Breast Cancer and Transplantation

“…For cancers that are ER positive, treatment with tamoxifen, a prodrug that competitively inhibits binding of estrogen at estrogen receptors, and aromatase inhibitors, which block the conversion of androgens to estrogen by the aromatase enzyme, in premenopausal and postmenopausal women may reduce the risk of disease relapses and death by 40% and 30%, respectively (48). For women whose cancers carry the amplification of the HER-2 gene, trastuzumab, a monoclonal antibody against the extracellular domain of the HER-2/neu receptor, is effective in improving disease free and overall survival (49). Targeted therapies to HER-2/neu are generally not nephrotoxic and do not interfere with the metabolism or clearance of immunosuppressive agents, although complications, including hypomagnesemia and increased risk of cardiovascular toxicity (in those with preexisting renal dysfunction), have been reported after treatment (50).…”

Critical Overview of HER2 Assessement in Bladder Cancer: What Is Missing for a Better Therapeutic Approach?

“…It is a proto-oncogene encoded by the ERBB2 gene in humans and is part of a large family of human epidermal growth factor receptors (together with HER1, HER3 and HER4) (19). Thirty years after its discovery and characterisation in breast cancer cells (20), HER2 represents a therapeutic target for more than 30% of metastatic breast cancer cases (21,22) but the function of this receptor is not fully elucidated yet. The plasticity of this molecular target to form heterodimers not only with other members of the EGFR family but also with other related RTKs seems to be one of the mechanisms responsible for resistance development following specific treatment with humanized monoclonal antibodies against HER2 such as trastuzumab (23).…”

Clinical Applications of Circulating Tumor Cells in Pharmacotherapy: Challenges and Perspectives

“…Variations in the expression of estrogen receptor and human epidermal growth factor receptor 2 can occur in advanced breast cancer, and has been readily detected in CTCs. Monitoring these changes is helpful when selecting chemotherapies, especially those targeting the human epidermal growth factor receptor, such as trastuzumab, lapatinib, pertuzumab, and trastuzumab-emtansine (Thompson et al, 2010;Aktas et al, 2011;Turner and Di Leo, 2013;Hernández-Blanquisett et al, 2016) . In addition, several therapeutic targets such as anaplastic lymphoma kinase (Ilie et al, 2012;Pailler et al, 2013), PD-L1 (Jing et al, 2016), and RAS (Karandish and Mallik, 2016), were also detected in CTCs collected from breast, colorectal, prostate, and ovarian cancer patients (Fig.…”