Initial testing (stage 1) of vorinostat (SAHA) by the pediatric preclinical testing program.
Vorinostat, a histone deacetylase inhibitor, was evaluated against the in vitro and in vivo childhood solid tumor and leukemia models in the Pediatric Preclinical Testing Program (PPTP). In vitro testing was performed by the DIMSCAN cytotoxicity assay. In vivo, vorinostat was administered intraperitoneally to mice bearing xenografts. Vorinostat demonstrated 2-log cell growth inhibitory activity in vitro, but generally at concentrations not sustainable in the clinic. No objective responses were observed for any of the solid tumor or acute lymphoblastic leukemia xenografts. Preclinical studies with appropriate drug combinations may provide direction for further clinical evaluations of vorinostat against selected pediatric cancers.
Children's Hospital of Los Angeles, Los Angeles, California 90027, USA. nkeshelava@chla.usc.edu
Nino
N
Keshelava
Peter J
PJ
Houghton
Christopher L
CL
Morton
Richard B
RB
Lock
Hernan
H
Carol
Stephen T
ST
Keir
John M
JM
Maris
C Patrick
CP
Reynolds
Richard
R
Gorlick
E Anders
EA
Kolb
Jianrong
J
Wu
Malcolm A
MA
Smith
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat