Background: Patients with organ transplants have a significantly increased risk of skin cancer, especially squamous cell carcinoma, as a result of long-term treatment with immunosuppressive drugs. This paper provides a brief overview of the assumed underlying mechanisms.
Method: The paper builds on relevant articles and studies identified in the course of many years of interest in immunopharmacology and skin cancer after organ transplantation.
Results: Reduced immunological tumour surveillance as a result of chronic immunosuppression has long been assumed to underlie the increased risk of skin cancer after organ transplants. Recent studies indicate that immunosuppressive drugs may also have specific carcinogenic effects. Aziatropine, which inhibits proliferation of lymphocytes, increases oxidative DNA damage caused by UV radiation. Ciclosporin and tacrolimus, which have an immunosuppressive effect by inhibiting calcineurin, promote malignant phenotypes in cell culture and tumour growth in mouse models. Calcineurin has proved to be necessary in order for p53 protein to have a protective effect against skin cancer. A relatively new class of immunosuppressive drugs, mTOR inhibitors, have antineoplastic properties and are associated with less risk of skin cancer. A number of randomised studies are currently in progress to see whether mTOR inhibitors can reduce the risk of skin cancer after organ transplantation.
Interpretation: Immunosuppressive drugs contribute to skin cancer after organ transplantation, either as a result of immunosuppression or through specific carcinogenic mechanisms. Immunosuppressive drugs with antineoplastic properties are now starting to be used.