Antitumor Activity of HM781-36B, alone or in Combination with Chemotherapeutic Agents, in XXXX .

@entity1 @entity38054 @entity470 @entity7952 @entity14 @entity694
Purpose: HM781-36B is a novel and irreversible pan- @entity1 @entity470 (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this study is to evaluate the antitumor activity and mechanism of action for HM781-36B in @entity14 cell lines. Materials and Methods: The @entity14 cell lines were exposed to HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell viability was examined by Cell Titer-Glo luminescent cell viability assay kit. Change in the cell cycle and protein expression was determined by flow cytometry and immunoblot analysis, respectively. Synergism between 2 drugs was evaluated by the combination index. Results: The addition of HM781-36B induced potent growth inhibition in both DiFi cells with @entity470 overexpression and SNU-175 cells (IC50 = 0.003 and 0.005    M, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, @entity7952 and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, @entity38054 . The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an additive or synergistic effect in most @entity14 cells. Conclusion: These findings suggest the potential roles of HM781-36B as the treatment for @entity470 -overexpressing @entity694 , singly or in combination with chemotherapeutic agents. The role of @entity38054 expression as a marker of response to HM781-36B should be further explored.
