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

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 Foun...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways and Cancer Metabolism: Poster Presentations - Proffered Abstracts Source Type: research