Skin Photodamage and Melanomagenesis: A Comprehensive Review
Michele Manganelli, Giorgio Stabile, Camila Scharf, Antonio Podo Brunetti, Giovanni Paolino, Roberta Giuffrida, Gianmarco Diego Bigotto, Giuseppe Damiano, Santo Raffaele Mercuri, Fabio Sallustio, Eleonora Mangano, Roberta Bordoni, Paola De Nardi, Gabriella Guida, Caterina Foti, Giuseppe Argenziano, Caterina Longo, Giovanni Pellacani, N. Rizzo, Vincenzo Russo, Stefania Guida, Franco Rongioletti
Abstract
Melanoma, the most aggressive form of skin cancer, still represents a significant and growing public health concern. Ultraviolet radiation (UVR) is considered the primary driver of melanoma, although genetic predisposition also plays a critical role. This review explores the intricate molecular mechanisms by which UVR-induced photodamage contributes to melanoma development. We examine epidemiological evidence linking UV exposure to increased risk, detailing how UVR damage to DNA triggers inflammatory responses and impairs DNA repair mechanisms. Specifically, we discuss the roles of nucleotide excision repair (NER) and base excision repair (BER) in mitigating UV damage. The review further explores diagnostic and surgical implications for melanomas arising on sun-exposed skin. By synthesizing current evidence, this overview aims to deepen understanding of the complex relationship between UVR, photodamage, and melanoma, shedding light on the need for personalized preventive strategies to better stratify the risk and introduce behavioral changes to reduce skin photodamage.