Skin cancer in organ transplant recipients: More than the immune system

Lee Wheless, Sarah Jacks, Kathryn Anne Mooneyham Potter, Brian C. Leach, Joel Cook

Research output: Contribution to journalReview article

28 Scopus citations

Abstract

Organ transplant recipients (OTRs) are at increased risk of developing nonmelanoma skin cancers. This has long been thought to be caused by immunosuppression and viral infection. However, skin cancer risk among individuals with AIDS or iatrogenic immunodeficiency does not approach the levels seen in OTRs, suggesting other factors play a critical role in oncogenesis. In clinical trials of OTRs, switching from calcineurin inhibitors to mammalian target of rapamycin inhibitors consistently led to a significant reduction in the risk of developing new skin cancers. New evidence suggests calcineurin inhibitors interfere with p53 signaling and nucleotide excision repair. These two pathways are associated with nonmelanoma skin cancer, and squamous cell carcinoma in particular. This finding may help explain the predominance of squamous cell carcinoma over basal cell carcinoma in this population. Mammalian target of rapamycin inhibitors do not appear to impact these pathways. Immunosuppression, viral infection, and impaired DNA repair and p53 signaling all interact in OTRs to create a phenotype of extreme risk for nonmelanoma skin cancer.

Original languageEnglish (US)
Pages (from-to)359-365
Number of pages7
JournalJournal of the American Academy of Dermatology
Volume71
Issue number2
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • calcineurin inhibitors
  • immunosuppression
  • mammalian target of rapamycin inhibitors
  • oncogenic viruses
  • organ transplant recipients
  • skin cancer

ASJC Scopus subject areas

  • Dermatology

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