Photocarcinogenesis and Skin Cancer Prevention Strategies: An Update

Abstract

UV radiation is acknowledged as the primary cause of photocarcinogenesis and therefore contributes to the development of skin cancer entities such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. Typical DNA photoproducts and indirect DNA damage caused by reactive oxygen species are the result of UV radiation. UV-induced DNA damage is repaired by nucleotide excision repair, which consequently counteracts the development of mutations and skin carcinogenesis. Tumour-suppressor genes are inactivated by mutation and growth-promoting pathways are activated leading to disruption of cell-cycle progression. Depending on the skin cancer entity, some genes are more frequently affected than others. In BCC mutations in Patched or Smoothened are common and affect the Sonic hedgehog pathway. In SCC, cell regulator protein p53 (TP53) mutations are prevalent, as well as mutations of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 2A (CDKN2A), Rat sarcoma (RAS), or the tyrosine kinase Fyn (FYN). UV-induced mutations in TP53 and CDKN2A are frequent in melanoma. UV-induced inflammatory processes also facilitate photocarcinogenesis. Recent studies showed a connection between photocarcinogenesis and citrus consumption, phytochemicals, alcohol consumption, hormone replacement therapy, as well as oral contraceptive use. Preventative measures include adequate use of sun protection and skin cancer screening at regular intervals, as well as the use of chemopreventative agents.

MMP-9 and IL-1β as Targets for Diatoxanthin and Related Microalgal Pigments: Potential Chemopreventive and Photoprotective Agents

“…In this context, compounds able to exert photochemopreventive activities are significant targets [ 31 , 32 , 33 ], since photochemoprevention might represent a valuable solution to prevent or limit the occurrence and the severity of UV-related diseases and photocarcinogenesis. The latter is linked to the multiple effects of UV radiation on skin [ 34 ], including photoaging, release of reactive oxygen species, DNA mutations, inflammation, and release of immunomodulatory cytokines. Efficacy of photochemopreventive effects depends on different factors, such as the ability of the molecule to absorb UVA and UVB rays [ 35 ], the antioxidant effect of the molecule and ROS scavenging, the inhibition of MMPs, which could damage or destroy the collagen and elastic fibers that constitute the dermis, and the modulation of stress-dependent signaling and/or suppression of cellular and tissue responses, such as inflammation and cytokines release [ 35 , 36 ].…”

The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene

“…There are several reports pointing to enhanced Ras signaling in βHPV-induced lesions independent of oncogenic mutations. Notably, Ras mutations have been shown to be present in only a subgroup of epithelial tumors on sun-exposed skin [63]. In clinical cSCC samples obtained from melanoma patients, which were treated with the Raf-inhibitor vemurafenib, H-Ras mutations and the presence of HPV were mutually exclusive [64].…”

Xeroderma Pigmentosum: Gene Variants and Splice Variants

“…Because UV-B radiation (280-315 nm) can be directly absorbed by DNA, it has a high mutagenic potential. UV-B radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs) and 6,4pyrimidine-pyrimidone dimers (6, within the DNA, so-called bulky lesions that distort the DNA backbone [1]. The nucleotide excision repair (NER) is essential for the repair of ultraviolet (UV)-associated DNA lesions.…”