부산대학교 도서관

Trastuzumab (Herceptin®) is currently used as a treatment for patients whose breast tumors overexpress HER2/ErbB2. Trastuzumab-DM1 (T-DM1, trastuzumab emtansine) is designed to combine the clinical benefits of trastuzumab with a potent microtubule-disrupting drug, DM1 (a maytansine derivative). Currently T-DM1 is being tested in multiple clinical trials. The mechanisms of action for trastuzumab include inhibition of PI3K/AKT signaling pathway, inhibition of HER-2 shedding and Fcγ receptor mediated engagement of immune cells, which may result in antibody-dependent cellular cytotoxicity (ADCC). Here we report that T-DM1 retains the mechanisms of action of unconjugated trastuzumab and is active against lapatinib resistant cell lines and tumors. Keywords Breast cancer * HER2 * ErbB2 * Trastuzumab * Therapeutic antibodies * Antibody drug conjugate (ADC) * Trastuzumab-DM1 (T-DM1)
Introduction HER2 positive breast cancer is a well-recognized subgroup of breast cancer [1]. Gene amplification of HER2 defines the class and this alteration manifests itself in the overexpression of HER2 [...]