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.

Keywords:

• androgen
• CYP3A4
• finasteride
• haplotype
• personalized medicine
• pharmacogenetics
• prostate cancer
• single nucleotide polymorphism
• SRD5A2
• UGT1A

Financial & competing interests disclosure

This work was supported in part by National Cancer Institute (NCI) grant PO1 CA108964 (project 1) to Juergen KV Reichardt who is also a Medical Foundation Fellow at the University of Sydney. This work was also supported by the Intramural Research Program of the NIH, NCI, Division of Cancer Epidemiology and Genetics, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported in part by National Cancer Institute (NCI) grant PO1 CA108964 (project 1) to Juergen KV Reichardt who is also a Medical Foundation Fellow at the University of Sydney. This work was also supported by the Intramural Research Program of the NIH, NCI, Division of Cancer Epidemiology and Genetics, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.