Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer

被引：461

作者：

Junttila, Teemu T. ^{[1
]}

Li, Guangmin ^{[1
]}

Parsons, Kathryn ^{[1
]}

Phillips, Gail Lewis ^{[1
]}

Sliwkowski, Mark X. ^{[1
]}

机构：

[1] Genentech Inc, Res Oncol, San Francisco, CA 94080 USA

来源：

BREAST CANCER RESEARCH AND TREATMENT | 2011年 / 128卷 / 02期

关键词：

Breast cancer; HER2; ErbB2; Trastuzumab; Therapeutic antibodies; Antibody drug conjugate (ADC); Trastuzumab-DM1 (T-DM1); ADJUVANT CHEMOTHERAPY; MONOCLONAL-ANTIBODY; BINDING-SITE; HUMAN IGG1; HERCEPTIN; THERAPY; PLUS; HER2; FC; MAYTANSINE;

D O I：

10.1007/s10549-010-1090-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Trastuzumab (Herceptin(A (R))) 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 Fc gamma 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.

引用

页码：347 / 356

页数：10

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