Format

Send to

Choose Destination
Expert Opin Investig Drugs. 2000 Dec;9(12):2923-34.

Modifying histones to tame cancer: clinical development of sodium phenylbutyrate and other histone deacetylase inhibitors.

Author information

1
The Johns Hopkins Oncology Center, Room 288, 1650 Orleans Street, Baltimore, Maryland 21231, USA. Steven.Gore@jhu.edu

Abstract

Compounds that inhibit histone deacetylase may enable the re-expression of silenced regulatory genes in neoplastic cells, reversing the malignant phenotype. Although several molecules that inhibit histone deacetylase are undergoing preclinical development, butyric acid derivatives have undergone clinical investigation for several years, initially for non-malignant indications and more recently for the treatment of cancer. Of the butyric acid derivatives, sodium phenylbutyrate has undergone the most extensive systematic investigation. Administration of phenylbutyrate by iv. and oral routes is well-tolerated clinically at concentrations which effect acetylation of histones in vitro. Higher doses lead to reversible CNS depression. The studies presented to date have been Phase I studies and do not enable assessment of efficacy. However, current development of phenylbutyrate is proceeding in combination with other agents based on rational biologically-based in vitro studies. The parallel development of combination therapy including phenylbutyrate and early clinical development of other, more potent histone deacetylase inhibitors will hopefully lead to feasible, clinically tolerable strategies for altering the malignant phenotype of cancer cells.

PMID:
11093362
DOI:
10.1517/13543784.9.12.2923
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center