Combination of AZD2281 (Olaparib) and GX15-070 (Obatoclax) results in synergistic antitumor activities in preclinical models of pancreatic cancer.

Abstract	In this study, we explored the antitumor activities of the PARP inhibitor AZD2281 (Olaparib) and the pan-Bcl-2 inhibitor GX15-070 (Obatoclax) in six pancreatic cancer cell lines. While both agents were able to cause growth arrest and limited apoptosis, the combination of the two was able to synergistically cause growth arrest and non-apoptotic cell death. Furthermore, in an in vivo xenograft model, the combination caused substantially increased tumor necrosis compared to either treatment alone. Our results support further investigation of the combination of Bcl-2 and PARP inhibitors for the treatment of pancreatic cancer.
Authors	Shaohua Chen, Guan Wang, Xiaojia Niu, Jianyun Zhao, Wenxi Tan, Hebin Wang, Lijing Zhao, Yubin Ge
Journal	Cancer letters (Cancer Lett) Vol. 348 Issue 1-2 Pg. 20-8 (Jun 28 2014) ISSN: 1872-7980 [Electronic] Ireland
PMID	24534203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Chemical References	BRCA1 Protein BRCA1 protein, human BRCA2 Protein BRCA2 protein, human Enzyme Inhibitors Indoles Phthalazines Piperazines Poly(ADP-ribose) Polymerase Inhibitors Proto-Oncogene Proteins c-bcl-2 Pyrroles Poly(ADP-ribose) Polymerases obatoclax olaparib
Topics	Animals Antineoplastic Combined Chemotherapy Protocols (pharmacology) Apoptosis (drug effects) BRCA1 Protein (genetics) BRCA2 Protein (genetics) Cell Line, Tumor Cell Proliferation (drug effects) Cell Survival (drug effects) Dose-Response Relationship, Drug Drug Synergism Enzyme Inhibitors (administration & dosage) Female Humans Indoles Mice, Inbred BALB C Mice, Nude Necrosis Pancreatic Neoplasms (drug therapy, enzymology, genetics, pathology) Phthalazines (administration & dosage) Piperazines (administration & dosage) Poly(ADP-ribose) Polymerase Inhibitors Poly(ADP-ribose) Polymerases (metabolism) Proto-Oncogene Proteins c-bcl-2 (antagonists & inhibitors, metabolism) Pyrroles (administration & dosage) Time Factors Xenograft Model Antitumor Assays

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