Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the pediatric preclinical testing program

Richard B. Lock; Hernan Carol; John M. Maris; Min H. Kang; C. Patrick Reynolds; E. Anders Kolb; Richard Gorlick; Stephen T. Keir; Catherine A. Billups; Raushan T. Kurmasheva; Peter J. Houghton; Malcolm A. Smith

doi:10.1002/pbc.24451

Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the pediatric preclinical testing program

Richard B. Lock, Hernan Carol, John M. Maris, Min H. Kang, C. Patrick Reynolds, E. Anders Kolb, Richard Gorlick, Stephen T. Keir, Catherine A. Billups, Raushan T. Kurmasheva, Peter J. Houghton, Malcolm A. Smith

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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 8.8nM, range 4.4-27.1nM). 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.

Original language	English (US)
Pages (from-to)	E42-E45
Journal	Pediatric Blood and Cancer
Volume	60
Issue number	7
DOIs	https://doi.org/10.1002/pbc.24451
State	Published - Jul 2013
Externally published	Yes

Keywords

Developmental therapeutics
Hsp90 inhibitors
Preclinical testing

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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10.1002/pbc.24451

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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 8.8nM, range 4.4-27.1nM). 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.",

keywords = "Developmental therapeutics, Hsp90 inhibitors, Preclinical testing",

author = "Lock, {Richard B.} and Hernan Carol and Maris, {John M.} and Kang, {Min H.} and Reynolds, {C. Patrick} and Kolb, {E. Anders} and Richard Gorlick and Keir, {Stephen T.} and Billups, {Catherine A.} and Kurmasheva, {Raushan T.} and Houghton, {Peter J.} and Smith, {Malcolm A.}",

year = "2013",

month = jul,

doi = "10.1002/pbc.24451",

language = "English (US)",

volume = "60",

pages = "E42--E45",

journal = "Medical and Pediatric Oncology",

issn = "1545-5009",

publisher = "Wiley-Liss Inc.",

number = "7",

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TY - JOUR

T1 - Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the pediatric preclinical testing program

AU - Lock, Richard B.

AU - Carol, Hernan

AU - Maris, John M.

AU - Kang, Min H.

AU - Reynolds, C. Patrick

AU - Kolb, E. Anders

AU - Gorlick, Richard

AU - Keir, Stephen T.

AU - Billups, Catherine A.

AU - Kurmasheva, Raushan T.

AU - Houghton, Peter J.

AU - Smith, Malcolm A.

PY - 2013/7

Y1 - 2013/7

N2 - 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 4.4-27.1nM). 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.

AB - 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 4.4-27.1nM). 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.

KW - Developmental therapeutics

KW - Hsp90 inhibitors

KW - Preclinical testing

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JF - Medical and Pediatric Oncology

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ER -

Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the pediatric preclinical testing program

Abstract

Keywords

ASJC Scopus subject areas

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