Abstract B14: Targeting heat shock protein 90 with ganetespib for the treatment of lymphoma

Abstract

Abstract Effective treatments for lymphoma remain a serious unmet medical need: the incidence of lymphoma continues to rise, and lyphoma tumors can relapse in patients who initially respond to treatment. Heat shock protein 90 (HSP90) has become an attractive therapeutic target in treating many cancers including blood cancers. In our study, we show that ganetespib, a clinically promising and actively investigated second-generation HSP90 inhibitor, dramatically reduced growth of a couple of different kinds of lymphoma, such as mantle cell lymphoma and Burkitt's lymphoma in a dose-dependent manner. It induced G2/M cell-cycle arrest and apoptosis in all studied cell lines, such as Ramos, Jeko-1, Granta-519, Raji, etc. Ganetespib significantly inhibited growth of xenograft tumors in vivo as a single agent or in combination with doxorubicin. Results of H&E staining, TUNEL assays, and immunohistochemistry staining of Ki-67 revealed significant differences in ganetespib-treated tumors. A panel of signaling network proteins with a hub of HSP90 were screened for the effects of ganetespib and these pathways were studied mechanistically. In summary, our data suggest that ganetespib can be potentially used for the molecularly targeted therapy of lyphoma patients. Acknowledgments: This work was supported by the Jiangsu Specially-Appointed Professor Program (to H. Liu); Jiangsu Recruitment Program of Leading Creative and Entrepreneurial Talents (to H. Liu and Z. Tu); National Natural Science Foundation 81402145 (to H. Liu) and 31471294 (to Z. Tu); Natural Science Foundation of Jiangsu Province BK20140572 (to H. Liu); Start-up Scientific Research Fund for the Returned Oversea Scholars from Chinese Ministry of Education (to Z. Tu); Senior Talent Start-up Funds of Jiangsu University 14JDG050 (to H. Liu) and 14JDG011 (to Z. Tu); Priority Academic Program Development of Jiangsu Higher Education Institutions (to School of Pharmacy and Institute of Life Sciences of Jiangsu University). Note: This abstract was not presented at the conference. Citation Format: Hanqing Liu, Zhiquan Liang, peishan Zhang, Jingjing Zhao, Lingling Ruan, Yongjin Lu, Dongsheng Shang, Ying Sun, Zhigang Tu. Targeting heat shock protein 90 with ganetespib for the treatment of lymphoma. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B14.