A Review Article on Pharmaceutical Approaches in Melanoma: Nanocarriers, Immunomodulation, and Targeted Therapy

Melanoma is an aggressive malignancy of melanocytes that, despite accounting for only a small fraction of skin cancers, is responsible for the majority of skin cancer–related deaths. Its incidence has shown a steady global rise, with significant demographic and geographic variations influenced by ultraviolet (UV) radiation, genetic predisposition, and lifestyle-related factors. Mutations in BRAF, NRAS, NF1, and c-KIT represent major oncogenic drivers, while signaling pathways such as MAPK/ERK and PI3K/AKT play central roles in tumor initiation, progression, and resistance to therapy. In addition, the tumor microenvironment, angiogenesis, and immune escape mechanisms further complicate clinical management. Early recognition of suspicious lesions using clinical tools, dermoscopy, histopathology, and molecular profiling is essential for timely diagnosis and accurate staging. While targeted therapies and immune checkpoint inhibitors have revolutionized the therapeutic landscape, limitations persist due to acquired resistance, immune-related adverse effects, relapse, and high treatment costs. The economic and psychosocial burden of melanoma is substantial, particularly in younger and middle-aged populations where years of life lost are significant. To address these challenges, novel and emerging therapeutic approaches are under extensive investigation. Nanotechnology-based formulations are being developed to enhance drug delivery and overcome resistance, while gene-editing technologies such as CRISPR-Cas9 hold potential for precise genetic targeting. Oncolytic viruses, personalized vaccines, and photodynamic or photothermal therapies provide additional avenues for durable control. Natural bioactive compounds and nutraceuticals, including polyphenols and marine-derived agents, offer complementary strategies with immunomodulatory and anti-metastatic effects. The integration of biomarkers, pharmacogenomics, and liquid biopsy techniques is advancing precision medicine and real-time monitoring of therapeutic outcomes. Overall, melanoma remains a major clinical and research priority. Future directions emphasize multimodal treatment strategies, biomarker-guided personalization, and cost-effective preventive interventions to reduce global disease burden and improve patient survival.