The clinical development of histone deacetylase inhibitors as targeted anticancer drugs Journal Article
| Author: | Marks, P. A. |
| Article Title: | The clinical development of histone deacetylase inhibitors as targeted anticancer drugs |
| Abstract: | Importance of the field: Histone deacetylase (HDAC) inhibitors are being developed as a new, targeted class of anticancer drugs. Area covered in this review: This review focuses on the mechanisms of action of the HDAC inhibitors, which selectively induce cancer cell death. What the reader will gain: There are 11 zinc-dependent HDACs in humans and the biological roles of these lysine deacetylases are not completely understood. It is clear that these different HDACs are not redundant in their activity. This review focuses on the mechanisms by which HDAC inhibitors can induce transformed cell growth arrest and cell death, inhibit cell mobility and have antiangiogenesis activity. There are more than a dozen HDAC inhibitors, including hydroxamates, cyclic peptides, benzamides and fatty acids, in various stages of clinical trials and many more compounds in preclinical development. The chemically different HDAC inhibitors may target different HDACs. Take home message: There are extensive preclinical studies with transformed cells in culture and tumor-bearing animal models, as well as limited clinical studies reported to date, which indicate that HDAC inhibitors will be most useful when used in combination with cytotoxic or other targeted anticancer agents. © 2010 Informa UK, Ltd. |
| Keywords: | signal transduction; unclassified drug; histone deacetylase inhibitor; review; nonhuman; antineoplastic agents; clinical trials as topic; gemcitabine; antineoplastic agent; neoplasms; mitosis; animals; mice; cell death; dna damage; dna repair; protein bcl 2; unindexed drug; apoptosis; gene expression; cell growth; antineoplastic combined chemotherapy protocols; drug resistance, neoplasm; protein bcl xl; cell line, tumor; gene expression regulation, neoplastic; drug mechanism; cyclin dependent kinase inhibitor 1b; protein mcl 1; tumor necrosis factor related apoptosis inducing ligand; vorinostat; histone deacetylase inhibitors; reactive oxygen species; reactive oxygen metabolite; 5 aza 2' deoxycytidine; zinc; floxuridine; angiogenesis inhibitors; antiangiogenic activity; n (2 aminophenyl) 4 [4 (3 pyridinyl) 2 pyrimidinylaminomethyl]benzamide; panobinostat; romidepsin; histone deacetylases; cell motility; cancer cell destruction; azacitidine; valproic acid; pivaloyloxymethyl butyrate; belinostat; mechanism of action; pci 24781; glucose metabolism; hdac inhibitor; suberoylanilide hydroxamic acid; givinostat; ros; 4 phenylbutyric acid; cyclin dependent kinase inhibitor 1; entinostat; fatty acid derivative; hydroxamic acid derivative; jnj 26481585; sb 639; thioredoxin; molecular targeted therapy |
| Journal Title: | Expert Opinion on Investigational Drugs |
| Volume: | 19 |
| Issue: | 9 |
| ISSN: | 1354-3784 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2010-09-01 |
| Start Page: | 1049 |
| End Page: | 1066 |
| Language: | English |
| DOI: | 10.1517/13543784.2010.510514 |
| PUBMED: | 20687783 |
| PROVIDER: | scopus |
| PMCID: | PMC4077324 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: EOIDE" - "Source: Scopus" |
