RNA Therapeutics in Skin Cancer: Emerging Strategies, Challenges, and Future Perspectives

Skin cancer is one of the most frequently diagnosed malignant diseases worldwide and represents a significant public health challenge. A comprehensive understanding of its natural history is essential for the development of effective preventive and therapeutic strategies. The skin, being the largest and most accessible organ of the human body, offers unique advantages for localized and targeted drug delivery, making it an attractive platform for innovative therapeutic interventions. Current therapeutic strategies for skin cancer include surgery, radiotherapy, topical treatments, cryotherapy, chemotherapy, and systemic options such as immunotherapy and targeted therapy for advanced disease. However, these modalities are often limited by tumor recurrence, development of drug resistance, immune-related adverse effects, and challenges associated with effective drug delivery to deeper skin layers. These limitations highlight the urgent need for less invasive, more precise, and durable treatment strategies. Although ribonucleic acid (RNA)-based therapeutics have been investigated for several decades, recent advances in molecular biology, chemical modification, and delivery technologies have enabled their emergence as clinically viable treatment modalities. RNA therapeutics offer several advantages, including high target specificity, the ability to modulate previously undruggable molecular pathways, reduced systemic toxicity, and the potential for multiplexed targeting within a single therapeutic platform. These features make RNA-based approaches particularly promising for dermatological applications, including skin cancer. This review systematically examines emerging RNA-based therapeutic approaches for skin cancer, including RNA interference, antisense oligonucleotides, and messenger RNA-based therapies. Additionally, it discusses key biological, technological, and translational challenges and explores strategies to overcome barriers to clinical implementation. Overall, RNA therapeutics represent a promising and transformative platform for advancing skin cancer treatment and improving dermatological care.