Navigating the pharmacological landscape of ultraviolet-induced mutations in skin carcinogenesis

Ultraviolet (UV) radiation is a known environmental carcinogen whose adverse effects continually contribute to the global burden of disease. One of its brutal effects manifests in the form of skin cancers – namely, basal cell carcinoma, squamous cell carcinoma, and melanoma, its more aggressive but rare counterpart. UV rays exert their effect by direct deoxyribonucleic acid (DNA) damage, diminishing the body’s natural protective repair mechanisms, paving the way for transforming healthy cells into cancerous ones and increasing their metastatic potential. This includes the transformation of typically protective melanin from an antioxidant to a pro-oxidant, inducing oxidative stress and leading to DNA damage in melanocytes. This damage disrupts key signaling pathways such as mitogen-activated protein kinase (MAPK), B-raf proto-oncogene, serine/threonine kinase (BRAF), rat sarcoma viral oncogene homolog (RAS), contributing significantly to melanoma genesis. Treatment strategies target elements involved in these pathways by different mechanisms, such as boosting immune cell components, inducing programmed cell death (apoptosis), inhibiting DNA synthesis pathways, and halting tumor progression, to name a few. The use of novel drugs that target the melanocortin-1 receptor pathway, toll-like receptor 4, and non-coding ribonucleic acid, as well as innovative therapies such as photodynamic therapy, reflects advancements in skin cancer treatment. The prevalence of melanoma steadily rises annually, prompting newer and more targeted approaches to medicine and education regarding skin protection. This literature review summarizes current knowledge regarding pharmacological approaches to skin cancer, focusing on complex molecular mechanisms affected by UV-induced damage. Rising prevalence and advancements in treatment modalities have warranted attention on this topic.