Skin cancer in solid organ transplant recipients: are mTOR inhibitors a game changer?

Abstract

While immunosuppressive agents are necessary to prevent the rejection of transplanted organs, and are a great medical success story for protecting against early allograft loss, graft and patient survival over the long term are diminished by side effects from these same drugs. One striking long-term side effect is a high rate of skin cancer development. The skin cancers that develop in transplant recipients tend to be numerous, as well as particularly aggressive, and are therefore a major contributor to morbidity and mortality in transplant recipients. An apparent reason for the high incidence of skin cancer likely relates to suppression of immune surveillance mechanisms, but other more direct effects of certain immunosuppressive drugs are also bound to contribute to cancers of UV-exposed skin. However, over the past few years, evidence has emerged to suggest that one class of immunosuppressants, mammalian target of rapamycin (mTOR) inhibitors, could potentially inhibit skin tumour formation through a number of mechanisms that are still being studied intensively today. Therefore, in light of the high skin cancer incidence in transplant recipients, it follows that clinical trials have been conducted to determine if mTOR inhibitors can significantly reduce these post-transplant skin malignancies. Here, the problem of post-transplant skin cancer will be briefly reviewed, along with the possible mechanisms contributing to this problem, followed by an overview of the relevant clinical trial results using mTOR inhibitors.