The Genomic Alterations of 5α-Reductases and Their Inhibitor Finasteride's Effect in Bladder Cancer

Anticancer Res. 2017 Dec;37(12):6893-6898. doi: 10.21873/anticanres.12152.

Abstract

Background/aim: Since androgens affect urothelial bladder cancer (UBC), we examined whether 5α-reductases (5-AR) have genomic alterations in UBC and whether 5α-reductase inhibitors (5-ARI) affect UBC.

Materials and methods: The cBioPortal was used to analyze genomic alternations of 5-ARs in UBC cancer genomic datasets. Next, we used the Taiwan National Health Insurance Research database to conduct a population-based case-control study to investigate the effect of a 5-ARI, finasteride on UBC incidence. We also performed an XTT assay to examine the direct effect of finasteride on UBC cells.

Results: We found that 5-AR genomic alternations were observed in 29% of UBC patients and patients with alternations had shorter disease-free survival. Also, the use of finasteride with >180 cDDDs reduced the risk of UBC. Finasteride could directly inhibit UBC cell growth.

Conclusion: Based on our findings, we concluded that 5-AR could be explored as a therapeutic target for UBC with 5-ARIs.

Keywords: 5α-reductase; Urothelial bladder cancer; androgen; dihydrotestosterone; finasteride.

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism*
  • 5-alpha Reductase Inhibitors / therapeutic use
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Female
  • Finasteride / therapeutic use*
  • Genomics / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism

Substances

  • 5-alpha Reductase Inhibitors
  • Finasteride
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase