Non-Melanoma Skin Cancer: Assessing the Systemic Burden of the Disease

The emergence of systemic therapies and photoprotection against non-melanoma skin cancer (NMSC) raises questions on the broader systematic impact of the disease. Personalized medicine involves a holistic patient approach, through which the evaluation of systemic biomarkers can reveal the interconnected aspects of patient health and tailored therapies. Cumulative UV exposure disrupts redox equilibrium and triggers inflammation and cutaneous immunosuppression, processes that contribute independently or via their interplay to cutaneous carcinogenesis. This systemic impact can be further reinforced by biomolecules derived from the NMSC microenvironment, fueling a continuous cycle of oxidative stress and inflammation in the organism. Regarding investigation of the systemic burden of NMSC, we conducted a narrative review focusing on parameters related to redox status, inflammation, and immune suppression observed in the blood components (serum, plasma, and erythrocytes) of NMSC patients. Our findings revealed an association of NMSC patients with perturbations of redox homeostasis, as evidenced by the decreased antioxidant activity, lower levels of non-enzymatic antioxidants, and increased byproducts of lipid, protein, and DNA oxidative damage. Additionally, NMSC patients presented augmented levels of pro-inflammatory interleukins, reduced anti-tumor biomolecule levels, and enhanced immune response markers, as well as elevated vitamin D levels. These systemic changes may lead to the association of NMSC with a higher risk of secondary malignancies in other organs. Overall, the findings of the present study suggest that NMSC affects systemic health beyond the skin, underscoring the need for a comprehensive and individualized approach to the management and monitoring of the patient.