Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer
Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer
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DOI：
10.1016/j.canlet.2011.01.010
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发表时间：
2011-03-28
期刊：
影响因子：
9.7
通讯作者：
Bang, Yung-Jue
中科院分区：
文献类型：
--
作者：
Nam, Hyun-Jin;Kim, Hwang-Phill;Bang, Yung-Jue
曲妥珠单抗是一种HER 2导向治疗，已在HER 2扩增的胃癌中显示出临床获益。本研究证明了HM 781 - 36 B（一种基于喹唑啉的不可逆pan-HER抑制剂）在HER 2扩增胃癌细胞（SNU 216和N87）中的体外和体内强效抗肿瘤活性。HM 781 - 36 B抑制HER家族及其下游信号分子的磷酸化，诱导细胞凋亡和G1期阻滞。此外，HM 781 - 36 B与化疗药物在HER 2扩增和HER 2非扩增胃癌细胞中均发挥协同作用。因此，HM 781 - 36 B可单独或与化疗药物联合用于治疗HER 2扩增胃癌。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Trastuzumab, a HER2 directed treatment has shown clinical benefit in HER2 amplified gastric cancer. This study demonstrated the potent antitumor activity of HM781-36B, a quinazoline-based irreversible pan-HER inhibitor, in HER2 amplified gastric cancer cells (SNU216 and N87) in vitro and in vivo. HM781-36B inhibited phosphorylation of HER family and downstream signaling molecules, and induced apoptosis and G1 arrest. Furthermore, HM781-36B exerted synergistic effects with chemotherapeutic agents in both HER2 amplified and HER2 non-amplified gastric cancer cells. Therefore, HM781-36B may be useful for the treatment of HER2 amplified gastric cancer alone or in combination with chemotherapeutic agents. (C) 2011 Elsevier Ireland Ltd. All rights reserved.