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Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the pediatric preclinical testing program
Author(s) -
Lock Richard B.,
Carol Hernan,
Maris John M.,
Kang Min H.,
Reynolds C. Patrick,
Kolb E. Anders,
Gorlick Richard,
Keir Stephen T.,
Billups Catherine A.,
Kurmasheva Raushan T.,
Houghton Peter J.,
Smith Malcolm A.
Publication year - 2013
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24451
Subject(s) - in vivo , medicine , hsp90 inhibitor , cancer research , in vitro , blood cancer , leukemia , pharmacology , cancer , hsp90 , biology , biochemistry , heat shock protein , microbiology and biotechnology , gene
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 rIC 50 8.8 nM, range 4.4–27.1 nM). 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: E42–E45. © 2013 Wiley Periodicals, Inc.