Abstract 2614: 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 lymphoma tumors can relapse in patients who initially respond to treatment. Heat shock protein 90 (HSP90) has become an attractive therapeutic target in treating many 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. Mechanistically, ganetespib caused pronounced decrease of expression of classic HSP90 client proteins. In summary, our data suggest that ganetespib can be potentially used for the molecularly targeted therapy of lymphoma patients. Citation Format: Zhigang Tu, Hanqing Liu, Jingjing Zhao, Peishan Zhang, Zhiquan Liang, Lingling Ruan, Yongjin Lu, Dongsheng Shang, Ying Sun, Lili Xu, Keping Chen, Quji Danzeng. Targeting heat shock protein 90 with Ganetespib for the treatment of lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2614. doi:10.1158/1538-7445.AM2015-2614