Understanding the Role and Clinical Applications of Exosomes in Gynecologic Malignancies: A Review of the Current Literature

SIMPLE SUMMARY: Gynecologic malignancies are those that affect the female reproductive organs, including the ovary, uterus, and cervix. Gynecologic malignancies as a group vary significantly in initial clinical presentation, degree and pattern of spread, and treatment modalities. Our knowledge of the role exosomes play in cancer growth and spread is expanding rapidly. The promise these nanovesicles hold in cancer diagnostics and therapeutics is undeniable, and may be the key to improving the diagnosis and treatment of gynecologic cancers. This paper serves to review laboratory techniques utilized in isolating and studying exosomes, the current state of understanding of exosomes in gynecologic malignancies, and the potential for clinical applications that exosomes may hold. ABSTRACT: Background: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. Literature Review: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. Conclusion: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies.