Synergism between mTOR pathway and ultraviolet radiation in the pathogenesis of squamous cell carcinoma and its implication for solid-organ transplant recipients

Nonmelanoma skin cancers (NMSCs) are the most common malignancies in the United States in immunocompetent patients. Among the solid-organ transplant recipients, NMSCs represent a significant disease burden, and they tend to be multiple and more aggressive. While the precise mechanisms responsible for the higher risk of developing cutaneous squamous cell carcinomas (SCCs) have not been completely elucidated, ultraviolet (UV) light has been established to be critical in initiation and promotion of tumor development. More recently, significant emphasis has been placed on the role of the mammalian target of rapamycin (mTOR) pathway in SCC pathogenesis. Furthermore, some studies have demonstrated the ability of mTOR inhibitors to decrease the incidence of new SCCs in the immunosuppressed transplanted patient population. In this review, we will highlight and examine the most recent available data on the role of UV radiation and its interaction with mTOR pathway signaling in SCC pathogenesis.