Unravelling the role of stem cell-derived exosomes in oral cancer treatment: A review

Introduction: Oral cancer is the sixteenth most prevalent cancer globally, with Asian countries accounting for two-thirds of cases. Despite advancements in surgery, chemotherapy, and radiotherapy, late diagnosis, the absence of specific biomarkers, and the high cost of treatment result in poor outcomes. Tumor recurrence remains a significant challenge, highlighting the need for innovative therapeutic strategies. One promising avenue is the study of exosomes, which carry biomolecules like proteins, lipids, DNA, RNA, and microRNA, playing a key role in intercellular communication and the tumor microenvironment. Stem-cell-derived exosomes could revolutionize cancer therapy by targeting tumors and modulating immune responses. MicroRNAs within these exosomes are crucial in cancer progression, metastasis, and aggressiveness, contributing to high recurrence rates in oral cancer. Methods: This review followed PRISMA-ScR guidelines to explore the therapeutic potential of stem cell-derived exosomes in oral cancer. A literature search in PubMed and Web of Science used terms related to "exosomes,""stem cells," and "oral cancer," including studies in English published before March 1, 2024. Original research, clinical trials, in vitro, and in vivo studies were selected; reviews and conference abstracts were excluded. Two reviewers independently screened and reviewed studies. Data extraction included study characteristics such as exosome origin, cargo, target cells, animal species, sample size, pathways, and primary outcomes. Results: This review included nine studies, all conducted in vitro, with six also encompassing in vivo experiments. Notably, four of these studies were conducted in China. Findings suggest that stem cell-derived exosomes are promising candidates for oral cancer therapy, playing key roles in reducing pro-inflammatory cytokines, inducing apoptosis, enhancing cytotoxicity, inhibiting angiogenesis, and reducing oral cancer cell proliferation. The studies examined various types of exosomes derived from different stem cell sources, including umbilical cord mesenchymal stem cells, cancer stem cells, and other relevant tumor-related cells. Conclusions: This review unravels the therapeutic potential of stem cell-derived exosomes as promising tools for oral cancer therapy. Exosomes derived from UC-MSCs, SHED, MenSCs, and hBMSCs reduce inflammation, induce apoptosis, and modulate angiogenesis and metastasis. Offering advantages over conventional treatments, such as low immunogenicity and targeted delivery, further research and clinical trials are essential to validate their safety, efficacy, and mechanisms.