The incidence of melanoma has continued to increase over the past 30 years. Hence, developing effective therapies to treat both primary and metastatic melanoma are essential. While advances in targeted therapy and immunotherapy have provided novel therapeutic options to treat melanoma, gene therapy may provide additional strategies for the treatment of metastatic melanoma clinically. This review focuses upon the challenges and opportunities that gene therapy provides for targeting melanoma. We begin with a discussion of the various gene therapy targets which are relevant to melanoma. Next, we explore the gene therapy clinical trials that have been conducted for treating melanoma. Finally, challenges faced in gene therapy as well as combination therapies for targeting melanoma, which may circumvent these obstacles, will be discussed. Targeted combination gene therapy strategies hold significant promise for developing the most effective therapeutic outcomes, while reducing the toxicity to noncancerous cells, and would integrate the patient's immune system to diminish melanoma progression. Next-generation vectors designed to embody required safety profiles and "theranostic" attributes, combined with immunotherapeutic strategies would be critical in achieving beneficial management and therapeutic outcomes in melanoma patients.
Keywords: Gene therapy; Immunotherapy; Melanoma; Oncolytic viruses.
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