Journal
CANCER LETTERS
Volume 302, Issue 2, Pages 155-165Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.01.010
Keywords
HM781-36B; Pan-HER inhibitor; Gastric cancer; Antitumor activity; Chemotherapeutic agents
Categories
Funding
- Hanmi Pharmaceutical Company [06-2006-275-0]
- Ministry for Health, Welfare Family Affairs [A091081]
- Ministry of Education, Science and Technology [2009-0093820]
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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.
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