Clinical studies of histone deacetylase inhibitors.
Over the last 5 years, a plethora of histone deacetylase inhibitors (HDACi) have been evaluated in clinical trials. These drugs have in common the ability to hyperacetylate both histone and nonhistone targets, resulting in a variety of effects on cancer cells, their microenvironment, and immune responses. To date, responses with single agent HDACi have been predominantly observed in advanced hematologic malignancies including T-cell lymphoma, Hodgkin lymphoma, and myeloid malignancies. Therefore, in this review we focus upon hematologic malignancies. Generally HDACi are well tolerated with the most common acute toxicities being fatigue, gastrointestinal, and transient cytopenias. Of note, few patients have been treated for prolonged periods of time and little is known about long-term toxicities. The use of the biomarker of histone hyperacetylation has been useful as a guide to target specificity, but generally does not predict for response and the search for more clinically relevant biomarkers must continue.
Prince
H Miles
HM
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Australia and University of Melbourne, Parkville, Victoria, Australia. miles.prince@petermac.org
Bishton
Mark J
MJ
Harrison
Simon J
SJ
D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D047630:Depsipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007211:Indoles; D000077767:Panobinostat; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides; D000077337:Vorinostat
D000903:Antibiotics, Antineoplastic; D001549:Benzamides; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D011725:Pyridines; D011743:Pyrimidines; D013449:Sulfonamides; C118739:entinostat; D000077337:Vorinostat; D000077767:Panobinostat; C523184:mocetinostat; C087123:romidepsin; C487081:belinostat