The development of differentiation agents for the treatment of prostate cancer.
Given their novel mechanisms of action and relatively favorable toxicity profiles, differentiation agents have been the focus of much investigation in the field of oncology. Among the most well studied of these agents in prostate cancer have been the retinoids, vitamin D, peroxisome-proliferator-activated receptor gamma (PPARgamma) ligands, and, most recently, the histone deacetylase (HDAC) inhibitors. While the clinical activity of these agents has been limited, several obstacles to the development of these novel drugs have become apparent. A lack of validated measures of outcome and uncertainty regarding the appropriate disease states in which to test these agents have led to difficulty in trial design. Furthermore, a better understanding of the biologic targets and genes manipulated by these therapies is required such that more potent and selective drugs may be developed. By overcoming these obstacles, the full potential of this therapeutic class may be realized.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Matt
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Galsky
W Kevin
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Kelly
D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D023281:Genomics; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D056918:Nuclear Receptor Coactivators; D011471:Prostatic Neoplasms / Q000209:etiology / Q000517:prevention & control*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000235:genetics; D012176:Retinoids / Q000627:therapeutic use; D012307:Risk Factors; D014157:Transcription Factors / Q000627:therapeutic use; D015533:Transcriptional Activation / Q000187:drug effects* / Q000235:genetics; D016896:Treatment Outcome; D014807:Vitamin D / Q000627:therapeutic use
D004273:DNA, Neoplasm; D056572:Histone Deacetylase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators; D018160:Receptors, Cytoplasmic and Nuclear; D012176:Retinoids; D014157:Transcription Factors; D014807:Vitamin D