title: Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the Pediatric Preclinical Testing Program.
abstract: 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 8.8 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.
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Randwick, NSW, Australia. rlock@ccia.unsw.edu.au
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lock
authors.forename: Hernan
authors.initials: H
authors.lastname: Carol
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Min H
authors.initials: MH
authors.lastname: Kang
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Keir
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Billups
authors.forename: Raushan T
authors.initials: RT
authors.lastname: Kurmasheva
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D014230:Triazoles / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; C533237:STA 9090; D014230:Triazoles