Rational combinations using HDAC inhibitors.
In addition to well-characterized genetic abnormalities that lead to cancer onset and progression, it is now recognized that alterations to the epigenome may also play a significant role in oncogenesis. As a result, epigenetic-modulating agents such as histone deacetylase inhibitors (HDACi) have attracted enormous attention as anticancer drugs. In numerous in vitro and preclinical settings, these compounds have shown their vast potential as single agent anticancer therapies, but unfortunately equivalent responses have not always been observed in patients. Given the pleiotropic effects HDACi have on malignant cells, their true therapeutic potential most likely lies in combination with other anticancer drugs. In this review we will focus on the anticancer effects of HDACi when combined with other cancer therapeutics with an emphasis on those combinations based on a strong molecular rationale.
Bots
Michael
M
Cancer Therapeutics Program, The Peter MacCallum Cancer Centre, East Melbourne Victoria, Australia.
Johnstone
Ricky W
RW
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors