Melanoma Chemoprevention: Current Status and Future Prospects

Abstract

The incidence of skin cancers, both non-melanoma as well as melanoma, are increasing in the United States. The ultraviolet radiation, mainly from sun, is considered the major cause for these neoplasms. While non-melanoma skin cancers are far more numerous, melanoma remains the most challenging. This is because melanoma can become extremely aggressive and its incidence is increasing worldwide due to lack of effective early detection, as well as disease recurrence, following both surgery and chemotherapy. Therefore, in addition to better treatment options, newer means are required to prevent melanomas from developing. Chemoprevention is a reasonable cost-effective approach to prevent carcinogenesis by inhibiting the processes of tumor initiation, promotion and progression. Melanoma is a progressive disease, which makes it very suitable for chemopreventive interventions, by targeting the processes and molecular pathways involved in the progression of melanoma. This review discusses the roles of various chemopreventive agents such as NSAIDs, statins, vitamins and dietary agents in melanoma and highlights current advancements and our perspective on future of melanoma chemoprevention. Although considerable preclinical data suggest that melanoma may be prevented or delayed by a numerous chemopreventive agents, we realize there are insufficient clinical studies evaluating their efficacy and long-term safety for human use.

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials

“…Exposure to vitamin A activates the nuclear retinoid receptors RAR and RXR (reviewed in Chhabra et al 40 ). Pre-clinical studies of vitamin A and its precursors (retinol and the carotenoid pro-vitamins for vitamin A including beta-carotene) for melanoma chemoprevention have found both growth inhibiting and growth promoting effects on human cell lines.…”

“…Many of the observed effects are thought to be mediated by the strong antioxidant properties of vitamin E and its ability to quench free radicals and inhibit lipid peroxidation (reviewed in Chhabra et al 40 ). Recent data, however, have shown that Trolox, a vitamin E analog, increased migration and invasion in human melanoma cell lines through effects on the glutathione system 57 .…”

“…Activities associated with the ligand-bound vitamin D receptor include heterodimerization with the RXR and subsequent activation of the retinoid pathway (reviewed in Chhabra et al 40 ).…”

“…The mechanisms by which EGCG protects against skin cancers are diverse and include promotion of cell cycle arrest and apoptosis and inhibition of angiogenesis, as well as anti-inflammatory, immunomodulatory, and anti-oxidant effects (reviewed in Chhabra et al 40 ). Studies in mice have shown that both topical and oral delivery of EGCG can confer protection against KC.…”

Effects and Mechanism of Nicotinamide Against UVA‐ and/or UVB‐mediated DNA Damages in Normal Melanocytes

“…Although 95% of UVB radiation is absorbed in the protective ozone layer in our outer environment, the remaining 5% inbound UVB is a potent genotoxic agent to impart considerable response in skin cells, including melanocytes. UVB penetrates as deep as the epidermal basal cell layer of the skin and induces DNA damage , particularly in the form of cyclobutane pyrimidine dimers (CPDs), which are an important source of mutations in UV‐induced melanoma . On the other hand, UVA is a potent driver of oxidative DNA damage in skin cells and can cause mutations by generating reactive oxygen species (ROS) that oxidize guanine at the 8th position to produce 8‐hydroxy‐2′‐deoxyguanosine (8oxoG) .…”