• The Emerging Role of Stem Cells in Melanoma Therapy: Opportunities and Challenges
  • Shabnam Fahim,1,*
    1. School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.


  • Introduction: Melanoma is the most aggressive form of skin cancer, accounting for the majority of skin cancer–related deaths despite representing a smaller fraction of total cases. Its incidence has been steadily increasing worldwide, and advanced stages are associated with high rates of metastasis and therapeutic resistance. Conventional treatment strategies have significantly improved patient outcomes, including surgical excision, chemotherapy, radiotherapy, and, more recently, targeted therapies and immune checkpoint inhibitors. However, many patients with metastatic melanoma eventually relapse due to the development of drug resistance, immune evasion, and heterogeneity within the tumor microenvironment. These limitations highlight the need for novel therapeutic strategies to provide more durable and effective responses. In recent years, stem cells have gained increasing attention in oncology because of their unique biological properties, including self-renewal, multilineage differentiation, and immunomodulatory effects. Among them, mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and neural crest–derived stem cells have demonstrated promising applications in cancer therapy. Their inherent tumor-homing ability, a process where stem cells selectively migrate toward tumor tissues, makes them ideal candidates for targeted drug delivery. Furthermore, stem cells can be genetically modified to act as vehicles for oncolytic viruses, cytokines, or suicide genes, enhancing antitumor activity. Beyond their direct anticancer roles, stem cells contribute to tissue regeneration and repair, particularly important in patients suffering from treatment-induced skin damage. This review aims to provide an updated overview of the role of stem cells in melanoma therapy, summarizing recent preclinical and clinical findings, highlighting their therapeutic potential, and addressing the challenges that remain in translating these approaches into routine clinical practice.
  • Methods: This review was conducted by searching PubMed, Scopus, and Web of Science databases using the keywords stem cells, melanoma, therapy, immunotherapy, drug delivery, and tumor microenvironment. Articles published between 2013 and 2025 were considered. Preclinical and clinical studies reporting the application of stem cells in melanoma treatment, either directly or as delivery platforms, were included. Reviews and meta-analyses were also examined to summarize current knowledge and highlight future perspectives.
  • Results: Preclinical and clinical evidence indicate that stem cells can exert therapeutic effects in melanoma through several mechanisms. Mesenchymal stem cells (MSCs) show strong tumor-homing ability, allowing them to deliver chemotherapeutic agents, cytokines, or nanoparticles directly to melanoma tissues, which improves drug retention and reduces systemic toxicity. Moreover, stem cells modulate the tumor immune microenvironment by influencing T cells, natural killer (NK) cells, and dendritic cells, enhancing antitumor immunity. Genetically engineered stem cells have also been used to express tumor-suppressor genes, oncolytic viruses, or suicide genes, providing targeted killing of melanoma cells and overcoming drug resistance. In addition, stem cell–based therapies support tissue repair and wound healing in patients undergoing surgical resection or radiation. Despite these benefits, concerns remain regarding the dual role of MSCs, variability among stem cell populations, and safety issues such as unwanted differentiation. Most findings remain limited to preclinical studies, with only a few early-phase clinical trials reporting preliminary safety and efficacy data.
  • Conclusion: Stem cells represent a promising avenue for the treatment of melanoma due to their tumor-targeting potential, capacity for immune modulation, and suitability as vehicles for gene and drug delivery. While preclinical findings are encouraging, the translation into clinical practice requires meticulous optimization of stem cell sources, engineering strategies, and safety profiles. This careful approach ensures that future treatments are effective and safe for patients. Future research should focus on integrating stem cell–based therapies with immunotherapy and nanotechnology to enhance therapeutic precision and reduce relapse. The development of standardized protocols and large-scale clinical trials will be critical in determining the real potential of stem cells in melanoma therapy.
  • Keywords: Stem cells; Melanoma; Mesenchymal stem cells; Immunotherapy; Drug delivery