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Review
. 2025 May 26;17(11):1784.
doi: 10.3390/cancers17111784.

Skin Photodamage and Melanomagenesis: A Comprehensive Review

Michele Manganelli  1 , Giorgio Stabile  2   3 , Camila Scharf  4 , Antonio Podo Brunetti  2   3 , Giovanni Paolino  3   5 , Roberta Giuffrida  6 , Gianmarco Diego Bigotto  2   3 , Giuseppe Damiano  7 , Santo Raffaele Mercuri  3   5 , Fabio Sallustio  8 , Eleonora Mangano  9 , Roberta Bordoni  9 , Paola De Nardi  10 , Gabriella Guida  1 , Caterina Foti  11 , Giuseppe Argenziano  4 , Caterina Longo  12   13 , Giovanni Pellacani  14 , Nathalie Rizzo  15 , Vincenzo Russo  7 , Stefania Guida  2   3 , Franco Rongioletti  2   3
Affiliations
Review

Skin Photodamage and Melanomagenesis: A Comprehensive Review

Michele Manganelli et al. Cancers (Basel). .

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.

Keywords: cumulative sun damage; melanoma; melanomagenesis; skin photodamage; ultraviolet radiation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The image illustrates the three main DNA repair mechanisms: (A) NER, (B) BER, and (C) TLS. XPC: Xeroderma Pigmentosum Complementation group C; HR23B: Homologous Recombination 23B; UV-DOB: UV-Damage DNA Binding; XPF-ERCC1: Xeroderma Pigmentosum Complementation group F-Excision Repair Cross-Complementation group 1; XPB: Xeroderma Pigmentosum Complementation group B; XPG: Xeroderma Pigmentosum Complementation group G; DNAPol: DNA Polymerase; PCNA: Proliferating Cell Nuclear Antigen; RNAPII: RNA Polymerase II; CSB: Cockayne Syndrome group B-protein; XPD: Xeroderma Pigmentosum Complementation group D; APE1: Apurinic/Apyrimidinic Endonuclease 1; Pol-β: DNA Polymerase β; XRCC1: X-Ray Repair Cross-Complementing protein 1; FEN1: Flap Endonuclease 1; Pol δ/ε: DNA Polymerases δ and ε; Ub: ubiquitin.
See this image and copyright information in PMC

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