Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma

Alessio Giubellino, Carole Sourbier, Min Jung Lee, Brad Scroggins, Petra Bullova, Michael Landau, Weiwen Ying, Len Neckers, Jane B. Trepel, Karel Pacak

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Metastatic pheochromocytoma represents one of the major clinical challenges in the field of neuroendocrine oncology. Recent molecular characterization of pheochromocytoma suggests new treatment options with targeted therapies. In this study we investigated the 90 kDa heat shock protein (Hsp90) as a potential therapeutic target for advanced pheochromocytoma. Both the first generation, natural product Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), and the second-generation synthetic Hsp90 inhibitor STA-9090 (ganetespib) demonstrated potent inhibition of proliferation and migration of pheochromocytoma cell lines and induced degradation of key Hsp90 clients. Furthermore, ganetespib induced dose-dependent cytotoxicity in primary pheochromocytoma cells. Using metastatic models of pheochromocytoma, we demonstrate the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival. Levels of Hsp70 in plasma from the xenograft studies served as a proximal biomarker of drug treatment. Our study suggests that targeting Hsp90 may benefit patients with advanced pheochromocytoma.

Original languageEnglish (US)
Article numbere56083
JournalPloS one
Volume8
Issue number2
DOIs
StatePublished - Feb 14 2013

Fingerprint Dive into the research topics of 'Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma'. Together they form a unique fingerprint.

  • Cite this

    Giubellino, A., Sourbier, C., Lee, M. J., Scroggins, B., Bullova, P., Landau, M., Ying, W., Neckers, L., Trepel, J. B., & Pacak, K. (2013). Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma. PloS one, 8(2), [e56083]. https://doi.org/10.1371/journal.pone.0056083