Biomarkers for predicting clinical responses to HDAC inhibitors.
Post-translational modifications of histone and non-histone proteins by acetylation are known to play a key role in tumourigenesis. Pharmacological manipulation of acetylation has been possible with the identification of small molecule inhibitors of histone deacetylases (HDAC), the enzymes responsible for deacetylating lysine residues. An explosion of drug discovery efforts in recent years has led to the development of an extensive group of HDAC inhibitors, many of which have been shown pre-clinically to have potent anti-tumour activity. Clinical trials using these agents are now underway, with Vorinostat (suberoylanilide hydroxamic acid) having been approved by the FDA for treating cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent or recurrent disease. This review discusses how biomarkers are being identified and used to expand our knowledge of the mechanisms by which HDAC inhibitors exhibit their anti-cancer effects. In the longer term, biomarkers will provide a means towards achieving patient stratification in tumour types that will respond favourably to HDAC inhibitors.
Dept of Clinical Pharmacology, Laboratory of Cancer Biology, Oxford, United Kingdom.
Lindsay
L
Stimson
Nicholas B
NB
La Thangue
D000107:Acetylation; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002986:Clinical Trials as Topic; D020869:Gene Expression Profiling; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011237:Predictive Value of Tests
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D008239:Lysine