title: Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer.
abstract: 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.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Nam
authors.forename: Hwang-Phill
authors.initials: HP
authors.lastname: Kim
authors.forename: Young-Kwang
authors.initials: YK
authors.lastname: Yoon
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Hur
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Song
authors.forename: Maeng-Sup
authors.initials: MS
authors.lastname: Kim
authors.forename: Gwan-Sun
authors.initials: GS
authors.lastname: Lee
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D066246:ErbB Receptors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C557213:HM781-36B