Could the use of melatonin be a promising complementary strategy in the prevention of skin cancer?

Abstract Skin cancer, including both non-melanoma and melanoma types, remains the most common neoplasm worldwide. Given its rising incidence, limitations of current therapies, and the challenges of effective prevention, novel therapeutic and preventive strategies are needed. One substance that has been the focus of growing attention is melatonin. This indolamine has garnered scientific interest due to its potential defensive effects against skin carcinogenesis. The aims of this article were to synthesize current evidence on the role of melatonin in the defense against skin cancer and propose its applicability as a preventive and adjuvant therapeutic agent to this type of cancer. A hypothesis-oriented narrative analysis was conducted using the MEDLINE/PubMed database, considering reviews and original articles published in English up to December 2025. Keywords related to melatonin, circadian rhythm, sleep disturbances, oxidative stress, and skin cancer biology were combined using Boolean operators. Experimental in vitro and in vivo studies, as well as available human data relevant to skin carcinogenesis were included. Beyond its participation in circadian rhythm regulation, melatonin exhibits antioxidant, anti-inflammatory, and immunomodulatory properties that directly influence skin cancer-related pathways. Evidence indicated that this indolamine protects against ultraviolet-induced DNA damage, modulates the tumor microenvironment, and regulates key molecular signaling cascades, like PI3K/Akt/mTOR and p53. Preclinical studies proposed that this hormone contributes to the control of oxidative imbalance, apoptosis, cell proliferation, and immune surveillance in both melanoma and non-melanoma skin cancer. We hypothesize that melatonin, owing to its diverse mechanisms of action, endogenous nature, and low toxicity at physiological levels or within targeted topical vehicles, may represent a promising complementary strategy for the prevention and adjuvant management of skin malignancies. Further clinical and experimental research is essential to validate the potential of this hormone as a novel agent in dermatologic oncology.