title: Finasteride metabolism and pharmacogenetics: new approaches to personalized prevention of prostate cancer.
abstract: Incidences of prostate cancer in most countries are increasing owing to better detection methods; however, prevention with the use of finasteride, a very effective steroid 5α-reductase type II inhibitor, has been met with mixed success. A wide interindividual variation in response exists and is thought to be due to heritable factors. This article summarizes the literature that attempts to elucidate the molecular mechanisms of finasteride in terms of its metabolism, excretion and interaction with endogenous steroid molecules. We describe previously reported genetic variations of steroid-metabolizing genes and their potential association with finasteride efficacy. Based on the literature, we outline directions of research that may contribute to understanding the interindividual variation in finasteride prevention and to the future development of personalized medicine.
authors.affiliation: University of Sydney, Bosch Institute, Camperdown, New South Wales, Australia.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Hulin-Curtis
authors.forename: Dominique
authors.initials: D
authors.lastname: Petit
authors.forename: W Douglas
authors.initials: WD
authors.lastname: Figg
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.forename: Juergen K V
authors.initials: JK
authors.lastname: Reichardt
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D058891:5-alpha Reductase Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D018120:Finasteride / Q000378:metabolism* / Q000493:pharmacokinetics; D014644:Genetic Variation; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D008297:Male; D057285:Precision Medicine; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control*; D013739:Testosterone / Q000378:metabolism
chemical_list: D058891:5-alpha Reductase Inhibitors; D013739:Testosterone; D018120:Finasteride; D051544:Cytochrome P-450 CYP3A; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D014453:Glucuronosyltransferase