P53 in skin cancer: From a master player to a privileged target for prevention and therapy.

The increasing incidence of skin cancer (SC) is a global health concern. The commonly reported side effects and resistance mechanisms have imposed the pursuit for new therapeutic alternatives. Moreover, additional preventive strategies should be adopted to strengthen prevention and reduce the rising number of newly SC cases. This review provides relevant insights on the role of p53 tumour suppressor protein in melanoma and non-melanoma skin carcinogenesis, also highlighting the therapeutic potential of p53-targeting drugs against SC. In fact, several evidences are provided demonstrating the encouraging outcomes achieved with p53-activating drugs, alone and in combination with currently available therapies in SC. Another pertinent perspective falls on targeting p53 mutations, as molecular signatures in premature phases of photocarcinogenesis, in future SC preventive approaches. Overall, this review affords a critical and timely discussion of relevant issues related to SC prevention and therapy. Importantly, it paves the way to future studies that may boost the clinical translation of p53-activating agents, making them new effective alternatives in precision medicine of SC therapy and prevention.