Journal
PEDIATRIC BLOOD & CANCER
Volume 60, Issue 7, Pages E42-E45Publisher
WILEY
DOI: 10.1002/pbc.24451
Keywords
developmental therapeutics; Hsp90 inhibitors; preclinical testing
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Funding
- National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
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Ganetespib, an Hsp90 inhibitor, was tested against the PPTP in vitro cell line panel and selected xenografts in vivo, including JAK2- and BRAF-mutated models. Ganetespib demonstrated potent in vitro cytotoxic activity (median rIC50 8.8nM, range 4.427.1nM). In vivo, ganetespib induced significant differences in EFS distribution for 4 of 11 xenografts. Intermediate activity (EFS T/C>2) was noted only for the MV4;11 xenograft, and there were no objective responses. Administered as single agents, Hsp90 inhibitors examined by the PPTP have shown limited evidence for a therapeutic window against both solid tumor and leukemia pediatric preclinical models. Pediatr Blood Cancer 2013; 60: E42E45. (c) 2013 Wiley Periodicals, Inc.
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