No causal link between phosphodiesterase type 5 inhibition and melanoma

Jenny Z. Wang, Stephanie Le, Claire Alexanian, Sucharita Boddu, Alexander Merleev, Alina Marusina, Emanual Maverakis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: To examine the association between phosphodiesterase type 5 (PDE5) inhibitor use and melanoma by 1) conducting a systematic review of observational studies; and 2) determining if low PDE5A gene expression in human melanoma correlated with decreased overall survival. Materials and Methods: A systematic search of observational studies examining the association between PDE5 inhibitor use and melanoma was performed through ClinicalTrials.gov, the Cochrane Library, EMBASE, PubMed, and Web of Science databases, and seven eligible studies were identified. PDE5A gene expression was analyzed with RNA sequencing data from 471 human melanoma samples obtained from The Cancer Genome Atlas. Results: Four studies reported a positive association between PDE5 inhibitor use and melanoma, and three studies found no correlation. RNA sequencing data analysis revealed that under-expression of the PDE5A gene did not impact clinical outcomes in melanoma. Conclusions: There is currently no evidence to suggest that PDE5 inhibition in patients causes increased risk for melanoma. The few observational studies that demonstrated a positive association between PDE5 inhibitor use and melanoma often failed to account for major confounders. Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting.

Original languageEnglish (US)
Pages (from-to)313-321
Number of pages9
JournalWorld Journal of Men?s Health
Volume37
Issue number3
DOIs
StatePublished - Sep 2019

Keywords

  • Melanoma
  • Phosphodiesterase 5 inhibitors
  • Sildenafil citrate
  • Tadalafil
  • Vardenafil dihydrochloride

ASJC Scopus subject areas

  • Reproductive Medicine
  • Urology
  • Psychiatry and Mental health
  • Public Health, Environmental and Occupational Health
  • Health Policy
  • Aging
  • Pharmacology (medical)

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