LAQV/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Clinical Academic Center of Coimbra, Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal.
Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188438. doi: 10.1016/j.bbcan.2020.188438. Epub 2020 Sep 24.
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.
皮肤癌 (SC) 的发病率不断上升，这是一个全球性的健康问题。常见的不良反应和耐药机制促使人们寻求新的治疗方法。此外，还应采取额外的预防策略，以加强预防并减少新的 SC 病例数量的上升。
这篇综述提供了有关 p53 肿瘤抑制蛋白在黑色素瘤和非黑色素瘤皮肤癌发生中的作用的相关见解，同时强调了针对 SC 的 p53 靶向药物的治疗潜力。事实上，提供了一些证据表明，单独使用 p53 激活药物以及与 SC 中目前可用的疗法联合使用，可以取得令人鼓舞的效果。另一个相关的观点是针对 p53 突变，因为在光致癌发生的早期阶段存在分子特征，作为未来 SC 预防方法的一部分。
总的来说，这篇综述对与 SC 预防和治疗相关的问题进行了批判性和及时的讨论。重要的是，它为未来的研究铺平了道路，这些研究可能会推动 p53 激活剂的临床转化，使它们成为 SC 治疗和预防精准医学的新有效选择。
