Melanoma is a highly aggressive skin cancer with over 100,000 new cases and nearly 8,000 deaths annually in the United States, representing a significant clinical and economic burden. While current therapies such as Vemurafenib offer initial benefit, rapid development of drug resistance and limited efficacy in early-stage interventions underscore the urgent need for alternative treatment strategies. The rising popularity of botanical and nutraceutical approaches—such as black salve, solasodine rhamnosyl glycosides, frankincense, cannabis, black raspberry, curcumin, milk thistle, and St. John’s Wort—reflects growing patient interest in plant-derived compounds as adjuncts or alternatives to conventional therapies. In this context, we propose the development of a scientifically validated, multi-compound transdermal patch for melanoma management.

Our approach begins with in silico identification of key melanoma driver mutations (BRAF, NRAS, KIT) and the selection of ribosomal S6 kinase 2 (RSK2) as a promising therapeutic target due to its central role in the MAPK pathway and cancer progression. Cannflavin A, B, and C—flavonoids from Cannabis sativa—are utilized as foundational scaffolds for RSK inhibition, with additional botanicals evaluated for synergistic effects. A modular retrosynthetic route enables efficient synthesis and optimization of these compounds. For drug delivery, hydrophilic polymers such as PVA, PVP, HPMC, or chitosan are employed to create a patch that forms a drug reservoir on the skin, ensuring controlled and sustained release. This targeted, non-invasive system has the potential to improve patient adherence, expand access, and reduce healthcare costs, addressing a critical unmet need in melanoma therapy while leveraging the expanding market for innovative, patient-friendly treatments.

Learning Objectives:

• Discover how botanical flavonoids (Cannflavin A/B/C) target RSK2 in melanoma

• Learn rational transdermal patch design for controlled botanical drug delivery

• Understand market impact and patient benefits of innovative melanoma therapies