مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Emerging Role of Extracellular Vesicles in Cancer Diagnosis and Therapy: Opportunities for Precision Medicine
Emerging Role of Extracellular Vesicles in Cancer Diagnosis and Therapy: Opportunities for Precision Medicine
Fateme Delbari,1Saba Safdarpour,2,*Ghazal Jebraeeli,3
1. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2. Department of Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 3. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Introduction: The three main subgroups of extracellular vesicles (EVs), based on their origin, are microvesicles/microparticles/ectosomes, which form through budding and separation from the plasma membrane; exosomes, which originate from the endosomal network and are released when multivesicular bodies merge with the plasma membrane; and apoptotic bodies, which are shed from apoptotic cells. EVs are found in body fluids such as serum, plasma, urine, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid, and they carry biological molecules from their cells of origin, including lipids, cytosolic and membrane proteins, and nucleic acids (DNA, RNA, miRNA, mRNA). EVs, by generating molecular signature patterns, can reveal the physiological status and diseases of the body. Since they can be analyzed through body fluids, they can be applied for non-invasive cancer diagnosis in a real-time and repeatable manner, serving as novel biomarkers. Unlike conventional biomarkers, which usually increase only in advanced stages of the disease and are limited in early cancer detection, these vesicles are also capable of identifying the disease at its early stages. The ability of EVs to transport therapeutic payloads and regulate tumor processes and immune responses has led to their being considered as an emerging tool in precision medicine.
The present study aimed to investigate the potential of EVs in cancer diagnosis and treatment, as well as to explore engineering methods to enhance their antitumor effects in the development of precision medicine.
Methods: We conducted a search on PubMed, ScienceDirect, Scopus, and Google Scholar using keywords including extracellular vesicles, cancer diagnosis, cancer therapy, precision medicine, and biomarkers for relevant publications from 2017 to 2025. From the seven papers, three were selected because they highlight the role of EVs in cancer-related applications within precision medicine. The remaining four were excluded because they did not offer pertinent details about the involvement of EVs.
Results: Studies have shown that EVs inhibit cancer cell growth through the transfer of regulatory RNA molecules (siRNA and miRNA) and also regulate angiogenesis, as exemplified by endothelial cell-derived EVs containing Delta-like 4 proteins and matrix metalloproteinases. Moreover, dendritic cell-derived EVs have proven effective in early clinical trials as a cell-free vaccine and maintenance immunotherapy for patients with nonoperable non-small cell lung cancer. EVs are also capable of delivering anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo, which ensures the stability of these agents and allows their efficient delivery to the bloodstream to exert their therapeutic effect. SMART-Exo and GEMINI-Exos are examples of multifunctional engineered EVs that simultaneously target cancer and immune cells, activate T cells, and enhance antitumor effects. In addition, decorating the EV surface with clinical antibodies (Fc-EVs) can recruit T cells and strengthen antitumor immune responses. Tumor-derived extracellular vesicles (tEVs) promote matrix remodeling and tumor progression by carrying extracellular matrix–degrading enzymes and heparinase, whereas using EVs as a decoy can capture tEVs, inhibit their enzyme activity, and limit cancer metastasis. EVs are also used as drug carriers in clinical applications, but challenges such as mass production, storage, purification, population heterogeneity, and selection of appropriate antigens for EV-based targeted therapy limit their widespread use.
Conclusion: Overall, EVs are capable of delivering cytokines, nucleic acids, costimulatory signals, vaccine adjuvants, and gene therapy vectors to cells. They play a significant role in regulating the immune response, the transfer of bioactive molecules, antigen presentation, and even the transmission of viruses and prions. Moreover, EVs can be used as a liquid biopsy approach for screening, monitoring treatment effectiveness, assessing tumor heterogeneity, and identifying minimal residual disease, as well as in immunotherapy with checkpoint inhibitors and vaccines. However, for cancer treatment, personalizing the application of EVs based on tumor type and stage, as well as patient characteristics, is essential, since cell heterogeneity and tumor microenvironment dynamics can limit their effectiveness. Additionally, resistance to therapy—arising from antigen mutations, the release of decoy EVs, or the transport of supportive molecules by cancer-associated fibroblasts—underscores the importance of multi-targeted strategies. Taken together, EVs offer promising opportunities for advancing precision medicine in cancer.
Keywords: Extracellular vesicles, precision medicine, cancer diagnosis, cancer therapy, biomarkers