Histone deacetylase inhibitors as anti-neoplastic agents.
Histone deacetylase inhibitors (HDACIs) constitute a novel class of targeted drugs that alter the acetylation status of histones and other important cellular proteins. These agents modulate chromatin structure leading to transcriptional changes, induce pleiotropic effects on functional pathways and activate cell death signaling in cancer cells. Anti-neoplastic activity in vitro was shown in several experimental models of cancer, but the exact mechanism of cytotoxicity and responses are not clearly understood. Phase I/II clinical trials of various HDACIs as single agents conducted to date have shown substantial activity in cutaneous T cell lymphoma (CTCL), preliminary activity in Hodgkin's disease and modest activity in myeloid neoplasms. Responses have been rare in solid tumors. Several agents are being tested in combination therapy clinical trials, either as chemosensitizers for cytotoxic chemotherapy or radiation therapy, or in association with DNA methylation inhibitors based on in vitro synergy. In this review, we focus on recent basic and clinical data that highlight the anti-neoplastic role of HDACIs.
Department of Leukemia, MD Anderson Cancer Center, Unit 428, Houston, TX 77030, USA.
Nicolas
N
Batty
Gabriel G
GG
Malouf
Jean Pierre J
JP
Issa
D000107:Acetylation; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002843:Chromatin / Q000378:metabolism; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects; D047630:Depsipeptides / Q000008:administration & dosage / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D000077337:Vorinostat
D000970:Antineoplastic Agents; D002843:Chromatin; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D000077337:Vorinostat; D014635:Valproic Acid; D006655:Histone Deacetylases