Drug insight: Histone deacetylase inhibitors - Development of the new targeted anticancer agent suberoylanilide hydroxamic acid Journal Article
| Authors: | Kelly, W. K.; Marks, P. A. |
| Article Title: | Drug insight: Histone deacetylase inhibitors - Development of the new targeted anticancer agent suberoylanilide hydroxamic acid |
| Abstract: | This review focuses on the discovery and development of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA). Post-translational modifications of the histones of chromatin are important factors in regulating gene expression - so-called epigenetic gene regulation. Acetylation and deacetylation of lysine residues in histone tails, controlled by the activities of HDACs and histone acetyltransferases, are among the most studied post-translational modification of histones. In addition to chromatin protein, transcription factors, cell-signaling regulatory proteins, and proteins regulating cell death are substrates of HDACs and may be altered in function by HDAC inhibitors. HDAC inhibitors have several remarkable aspects. For instance, despite HDACs being ubiquitously distributed through chromatin, SAHA selectively alters the transcription of relatively few genes, and normal cells are at least 10-fold more resistant than transformed cells to SAHA and related HDAC inhibitor-induced cell death. HDAC inhibitors represent a relatively new group of targeted anticancer compounds, which are showing significant promise as agents with activity against a broad spectrum of neoplasms, at doses that are well tolerated by cancer patients. SAHA is one of the HDAC inhibitors most advanced in development. It is in phase I and II clinical trials for patients with both hematologic and solid tumors. |
| Keywords: | signal transduction; protein expression; treatment outcome; unclassified drug; acute granulocytic leukemia; fludarabine; histone deacetylase inhibitor; clinical trial; review; squamous cell carcinoma; drug potentiation; nonhuman; solid tumor; drug targeting; antineoplastic agent; neoplasms; nonhistone protein; cell death; imatinib; apoptosis; bortezomib; multiple myeloma; protein targeting; transcription factor; genetic transcription; antineoplastic activity; drug structure; enzyme activity; kidney carcinoma; gene expression regulation; b cell lymphoma; t cell lymphoma; hematologic malignancy; protein processing; protein processing, post-translational; head and neck cancer; enzyme inhibitors; epigenetics; histone; chromatin; drug response; hematologic malignancies; mesothelioma; vorinostat; hydroxamic acids; thyroid cancer; flavopiridol; drug bioavailability; anthracycline derivative; structure analysis; drug dose regimen; histones; histone deacetylases; drug protein binding; clinical trials; lysine; valproic acid; solid tumors; histone deacetylase; deacetylation; 3 phenylsulfamoylcinnamohydroxamic acid; arylbutyric acid derivative; n (2 aminophenyl) 4 (3 pyridinylmethoxycarbonylaminomethyl)benzamide; 4 [n (2 hydroxyethyl) n [2 (3 indolyl)ethyl]aminomethyl]cinnamohydroxamic acid; 4 n acetyldinaline; trichostatin a; acetylation; regulator protein; carboxycinnamic acid bishydroxamide; thioredoxin; histone acetyltransferase; 17 allylamino 17 demethoxygeldanamycin; fr 901228; lbh 589a |
| Journal Title: | Nature Clinical Practice Oncology |
| Volume: | 2 |
| Issue: | 3 |
| ISSN: | 1743-4254 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-03-01 |
| Start Page: | 150 |
| End Page: | 157 |
| Language: | English |
| DOI: | 10.1038/ncponc0106 |
| PUBMED: | 16264908 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 195" - "Export Date: 24 October 2012" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work