Tucatinib (Tukysa) An Oral, Selective HER2 Inhibitor for the Treatment of HER2‐positive Solid Tumors

Tucatinib was an oral highly selective human epidermal growthfactor receptor-2 (HER-2) tyrosine kinase inhibitor, developed by Seattle Genetics. Tucatinib offers a promising therapeutic strategy for the treatment of HER-2-positive breast cancer with improved treatment efficacy and safety in combination with trastuzumab and capecitabine. HER2-directed kinase inhibitors can compete with ATP, resulting in the blockade of phosphorylation and preventing activation of downstream signaling pathways. The binding of HER proteins with their ligands triggers the formation of homodimers and heterodimers, which upregulate downstream signaling pathways. HER2 overexpression is also detected in other types of human cancers, including bladder, colon, ovary, esophagus, stomach, lung, uterus, and prostate cancer. Although the treatment of the patient with trastuzumab could improve prognosis in patients with HER2-positive metastatic breast cancer, primary and acquired resistance remains a significant clinical challenge in most patients with HER2-amplified metastatic breast cancer.