Phenylacetate and phenylbutyrate as novel, nontoxic differentiation inducers.
Phenylacetate and analogs represent a new class of pleiotropic growth regulators that alter tumor cell biology by affecting gene expression at both the transcriptional and post transcriptional levels. Based on these findings, NaPA and NaPB entered clinical trials at the National Cancer Institute. Ongoing phase I studies with NaPA, involving adults with prostate and brain cancer, have confirmed that therapeutic levels can be achieved with no significant toxicities, and provide preliminary evidence for benefit to patients with advanced disease (Thibault et al., submitted).
Samid
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D
Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Hudgins
W R
WR
Shack
S
S
Liu
L
L
Prasanna
P
P
Myers
C E
CE
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy; D002454:Cell Differentiation / Q000187:drug effects*; D017321:Clinical Trials, Phase I as Topic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D010648:Phenylacetates / Q000494:pharmacology* / Q000627:therapeutic use*; D010654:Phenylbutyrates / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D010648:Phenylacetates; D010654:Phenylbutyrates; C025136:phenylacetic acid