Background: Skin cancer is the most common cancer in the USA. Therefore, it is important to review the contribution of ultraviolet radiation (UVR) exposure to skin cancer in individuals with the highest risk. Documenting the relationship between outdoor sports solar ultraviolet exposure and their risk of skin cancer along with appropriate risk mitigation strategies can help inform clinicians of practical information for counseling sun protective behaviors in this population. Methods: We conducted a review of the current evidence using PubMed to answer the following research questions: (1) How is ultraviolet radiation measured? (2) What is the modern utility of the ultraviolet index in modifying recreational sun protection behaviors? (3) What is the risk of developing skin cancer for outdoor sport participants? (4) What is the prevalence of skin cancer in sport participants? and (5) Is the number of nevi and solar lentigines elevated in outdoor sport participants? Results: Based on the literature, individuals who practice outdoor sport-related activities receive high ultraviolet radiation exposure, have a high risk for skin cancer, have a high prevalence for pigmented lesions, and may benefit from electronic sun protection educational interventions. Conclusions: Individuals who practice outdoor sports experience substantially higher ultraviolet radiation exposure, routinely exceed the recommended exposure limits, and are at a higher risk of developing skin cancer. Therefore, those who are frequently engaged in outdoor leisure activities should be coached about efficient sun protective practices and relevant mobile technologies that may facilitate adherence.

Chemotherapeutic drugs are primarily administered to cancer patients via oral or parenteral routes. The use of transdermal drug delivery could potentially be a better alternative to decrease the dose frequency and severity of adverse or toxic effects associated with oral or parenteral administration of chemotherapeutic drugs. The transdermal delivery of drugs has shown to be advantageous for the treatment of highly localized tumors in certain types of breast and skin cancers. In addition, the transdermal route can be used to deliver low-dose chemotherapeutics in a sustained manner. The transdermal route can also be utilized for vaccine design in cancer management, for example, vaccines against cervical cancer. However, the design of transdermal formulations may be challenging in terms of the conjugation chemistry of the molecules and the sustained and reproducible delivery of therapeutically efficacious doses. In this review, we discuss the nano-carrier systems, such as nanoparticles, liposomes, etc., used in recent literature to deliver chemotherapeutic agents. The advantages of transdermal route over oral and parenteral routes for popular chemotherapeutic drugs are summarized. Furthermore, we also discuss a possible in silico approach, Formulating for Efficacy™, to design transdermal formulations that would probably be economical, robust, and more efficacious.

The eukaryotic translation initiation factor 4F complex (eIF4F) is a potential chemotherapeutic target in triple-negative breast cancer (TNBC). This complex regulates cap-dependent translational initiation and consists of three core proteins: eIF4E, eIF4G, and eIF4A1. In this study, we focus on repositioning compounds as novel inhibitors of eIF4A1-mediated translation. In order to accomplish this goal, a modified synthetic reporter assay was established. More specifically, a (CGG)4 motif, which confers eIF4A dependency, was incorporated into the 5’-leader region of a luciferase-tdTomato lentiviral reporter construct. The Prestwick Chemical Library was then screened in multiple TNBC cell lines by measuring the tdTomato fluorescent intensity. We identified several cardiac glycosides as potential inhibitors of eIF4A1-mediated translation. Based on our studies, we find that cardiac glycosides inhibit the expression of eIF4A1. To identify a potential mechanism by which this was occurring, we utilized the Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our pursuits led us to the discovery that cardiac glycosides also decrease levels of c-MYC. Quantitative PCR confirmed that decreases in c-MYC and eIF4A were occurring at the transcriptional level. As such, disruption of the eIF4A1-c-MYC axis may be a viable approach in the treatment of TNBC. The novel combination of rocaglamide A and digoxin exhibited synergistic anti-cancer activity against TNBC cells in vitro. The findings in this study and others are important for formulating potential combination chemotherapies against eIF4A1 in vivo. Thus, drug repositioning may be one classical approach to successfully target eIF4A1 in TNBC patients.

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