Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer

Abstract

Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. Malignant melanoma (MM) is less frequent but more lethal than NMSC. Given the individual and social burdens of skin cancers, performing an adequate prevention is needed. Ultraviolet (UV) ray exposure is one of the main risk factors for skin cancer. Thus, the first-choice prevention strategy is represented by photoprotection that can be both topical and systemic. The latter consists of the oral administration of molecules which protect human skin against the damaging effects of UV rays, acting through antioxidant, anti-inflammatory, or immunomodulator mechanisms. Although several compounds are commonly used for photoprotection, only a few molecules have demonstrated their effectiveness in clinical trials and have been included in international guidelines for NMSC prevention (i.e., nicotinamide and retinoids). Moreover, none of them have been demonstrated as able to prevent MM. Clinical and preclinical data regarding the most common compounds used for systemic photoprotection are reported in this review, with a focus on the main mechanisms involved in their photoprotective properties.

Keywords: basal cell carcinoma; melanoma; non-melanoma; photoprotection; squamous cell carcinoma.

Figure 1

This figure details the main mechanisms involved in the chemopreventive action of the drugs included in this review. Vit D interacts with vit D receptor (VDR) leading to the formation of a complex which migrates into the nucleus, interacts with DNA, and modulates the expression of cell cycle key regulators. NAM prevents UV-induced ATP depletion and is a precursor of NAD, an enzymatic cofactor, which mediates electron transfer by oscillating between its reduced (NADH) and oxidized (NAD+) states. The latter works as a substrate for PARP, a nuclear enzyme involved in DNA repair processes. PLE, Astaxanthin (ASX), and β-carotene are antioxidant agents that neutralize ROS, leading to the restoration of molecular oxygen. Retinoids interact with retinoid receptors (RAR or RXR) in the nucleus, thus leading to the formation of RARE complex. This latter acts as transcriptional factor for genes involved in cellular differentiation, growth arrest, and apoptosis. Celecoxib is an anti-inflammatory drug, inhibitor of cyclooxygenase−2 (COX2), and a key enzyme in the synthesis of prostaglandins (PGE₂) from arachidonic acid (Ar Ac).