bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2025–06–22
six papers selected by
Muhammad Rizwan, COMSATS University
  1. Current trends in theranostic applications of extracellular vesicles in cancer.
  2. Exosomes: a potential tool in the diagnosis, prognosis and treatment of patients with colorectal cancer.
  3. Exosomes in hypoxia: generation, secretion, and physiological roles in cancer progression.
  4. Evaluation of Organoid-Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross-Sectional Study.
  5. Cancer-Derived Exosomal LINC01615 Induces M2 Polarization of Tumor-Associated Macrophages via RBMX-EZH2 Axis to Promote Colorectal Cancer Progression.
  6. Plasma-derived exosomal human epidermal growth factor receptor 2 (HER2) protein for distinguishing breast cancer from benign breast disease and assessing the efficacy of neoadjuvant therapy.
  1. Front Oncol. 2025 ;15 1592006
    Current trends in theranostic applications of extracellular vesicles in cancer.
    Yazan Almasry, Fayrouz Mustafa, Mohammed Alfuwais, Sara AlNachef, Hager Mohamed, Nusaibah S Gaber, Mohammed Imran Khan, Islam M Saadeldin, Ahmed Yaqinuddin.
       Background: Extracellular vesicles (EVs) play an integral role in cancer biology, influencing tumor progression, metastasis, and tumor microenvironment. Due to their distinctive molecular composition, including proteins, nucleic acids, and lipids, EVs present a promising candidate for cancer diagnostics and precision therapeutics.
    Methods: This review was conducted by looking up recent studies obtained through PubMed, Scopus, and Web of Science databases using targeted keywords such as "Extracellular Vesicles," "Cancer Therapy," "Biomarkers," "Exosomes," "Tumor Microenvironment," and "Precision Medicine." From an initial 4,320 articles identified, 427 were screened after applying publication filters, resulting in the inclusion of 298 articles relevant to EV isolation, characterization, diagnostic sensitivity, specificity, and therapeutic efficacy.
    Results: Biomarkers derived from EVs derived across various cancers showed high diagnostic performance. For example, four miRNA EVs showing sensitivity and specificity of 98% and 96% respectively was found in breast cancer. EV-RNA and surface antigen analyses for hepatocellular carcinoma with 93.8% sensitivity and 74.5% specificity. Additionally, EV biomarker cancers of the colorectal microRNA miR-23a and miR-301a had 89% sensitivity and >70% specificity. EVs in a therapeutic context were an effective drug delivery system for enhancing precision of chemotherapy and immunotherapy with reduced systemic toxicity.
    Conclusion: The theranostics of EVs provide great capacity for early cancer diagnosis and personalized treatment based on their high diagnostic sensitivity and specificity. Future standardization protocols are essential to translate EV technologies into clinical oncology.
    Keywords:  biomarkers; cancer therapy; exosomes; extracellular vesicles; precision medicine; tumor microenvironment
    DOI:  https://doi.org/10.3389/fonc.2025.1592006
  2. Future Oncol. 2025 Jun 14. 1-19
    Exosomes: a potential tool in the diagnosis, prognosis and treatment of patients with colorectal cancer.
    Azmin Akter, Tasnima Kamal, Sharmin Akter, Abdul Auwal, Farhadul Islam.
      Colorectal cancer (CRC), a commonly diagnosed malignancy, is one of the most frequent causes of cancer-related deaths worldwide. To effectively lower the death rate from this disease, it is essential to create public health methods, including developing new biomarkers that facilitate screening, diagnosis, prognosis, and therapy response prediction. CRC-derived Exosomes are a type of extracellular vesicle that transport functional molecules like proteins, lipids, nucleic acids (DNA, mRNA, miRNA, lncRNA, and noncoding RNA), and other metabolites, which act as molecular cargos to facilitate transportation. Exosomes generated and secreted from cancer cells are key biomarkers for early, noninvasive cancer diagnosis, prognosis, and treatment response, with their biogenesis in CRC offering molecular insights. Their expression varies across time, tissues, and disease stages. Thus, the development of innovative and effective techniques for isolating and detecting exosomes holds great potential for tumor diagnosis, prognosis prediction, and developing techniques (MSC-derived exosome, DC-derived exosome, engineered exosome, etc.) and their contents to improve the specificity and efficacy of therapies for patients with CRC. This review explores the features and formation of CRC-derived exosomes, highlighting their diagnostic, prognostic, and therapeutic significance through a comprehensive analysis of exosome extraction, identification, purification, and documented biological roles in existing literature.
    Keywords:  Colorectal cancer; biomarker; diagnosis; exosome; prognosis; therapy delivery
    DOI:  https://doi.org/10.1080/14796694.2025.2520150
  3. Front Immunol. 2025 ;16 1537313
    Exosomes in hypoxia: generation, secretion, and physiological roles in cancer progression.
    Yufeng Mu, Mengrui Yang, Jingyang Liu, Yan Yao, Huimin Sun, Jing Zhuang.
      The hypoxic microenvironment represents a universal hallmark feature of most solid tumors, profoundly shaping cancer progression through multifaceted mechanisms. Acting as nanoscale molecular envoys, exosomes transport oncogenic cargoes (including non-coding RNAs, mutated proteins, and metabolites) to reprogram stromal cells, prime pre-metastatic niches, and establish tumor-host metabolic symbiosis. Their lipid bilayer architecture ensures the protection of labile hypoxia-responsive factors, positioning them as critical amplifiers of intercellular crosstalk within the tumor microenvironment. Despite significant advances, critical gaps persist in understanding the spatiotemporal regulation of exosomal release under hypoxia, particularly the organ-specific variations in hypoxic exosome signatures revealed by single-vesicle analyses. This review synthesizes recent advances in the intricate interplay between hypoxia and exosomes, emphasizing hypoxia-related signaling pathways that directly modulate exosome biogenesis and indirectly activate hypoxia-associated microenvironmental remodeling, alongside their distinct regulatory effects on exosomal cargo composition. Furthermore, it delineates the pivotal role of hypoxia-specific exosomes in driving cancer malignancy, including metastatic dissemination, immune evasion, and therapy resistance. By integrating molecular mechanisms with clinically actionable insights, this work establishes a translational framework for targeting the hypoxic exosome network in precision oncology, offering strategic references for biomarker discovery and therapeutic development.
    Keywords:  TME (tumor microenvironment); exosomes; hypoxia; oncogenic cargoes; tumor
    DOI:  https://doi.org/10.3389/fimmu.2025.1537313
  4. Clin Transl Sci. 2025 Jun;18(6): e70270
    Evaluation of Organoid-Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross-Sectional Study.
    Atsuhiro Sasaki, Masatake Kuroha, Masaki Tosa, Seiichi Takahashi, Shinya Oomori, Eiki Nomura, Tatsuya Kikuchi, Motoyuki Onodera, Yuichiro Sato, Teruko Miyazawa, Hirofumi Chiba, Naonobu Yokoyama, Jun Kusaka, Daisuke Okamoto, Tomoyuki Handa, Mikako Sugimura, Masahiro Iwabuchi, Keiichiro Hiramoto, Hidekazu Shirota, Hideya Iwaki, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune.
      Exosomal microRNAs (miRNAs) are candidates for liquid biopsies. Organoid culture systems enable long-term expansion of the colon epithelium. This study evaluated exosomal miRNAs from colorectal cancer organoids for liquid biopsy. Organoids were established from normal colon and colorectal cancer tissues. Exosomes were isolated from conditioned media. miRNAs were extracted from exosomes and compared using microarray analysis. Exosomal miRNAs expression levels in the sera of healthy patients and patients with colorectal cancer were compared at a single institution. The multicenter study was validated using miRNAs upregulated in the serum of colorectal cancer patients, along with exosomal miRNAs reported to be upregulated in colorectal adenoma organoids and sera. A total of 44 exosomal miRNAs were commonly expressed in both normal colorectal epithelial cells and colorectal cancer organoids, whereas 59 were exclusively expressed in colorectal cancer organoids. In a single-center cohort study, two exosomal miRNAs (miR-4284 and miR-5100) were upregulated in the serum of colorectal cancer patients. In a multicenter study, four exosomal miRNAs (miR-4284, miR-5100, miR-1246, and miR-1290) were upregulated in the serum of patients with colorectal cancer. The combination of these four exosomal miRNAs had comparable diagnostic performance to carcinoembryonic antigen, with an area under the curve of 0.75 (95% confidence interval: 0.65-0.83) versus 0.79 (95% confidence interval: 0.70-0.87). Combining the four miRNAs with carcinoembryonic antigen improved diagnostic accuracy, with an area under the curve of 0.82 (95% confidence interval: 0.74-0.89). Exosomal miRNAs derived from colorectal cancer organoids can serve as diagnostic biomarkers for colorectal cancer.
    Keywords:  carcinoembryonic antigen; miR‐1246; miR‐1290; miR‐4284; miR‐5100
    DOI:  https://doi.org/10.1111/cts.70270
  5. Int J Nanomedicine. 2025 ;20 7343-7358
    Cancer-Derived Exosomal LINC01615 Induces M2 Polarization of Tumor-Associated Macrophages via RBMX-EZH2 Axis to Promote Colorectal Cancer Progression.
    Anshu Li, Jiaxin Hong, Xianxiong Ma, Yongzhou Huang, Qi Jiang, Chenggang Zhang, Yu Wang, Yongming Huang.
       Background: LncRNAs have been proved to play an important role in human cancers. The M2 polarization of tumor associated macrophages (TAMs) is also reported to promote cancer progression. However, the specific role of cancer derived exosomal lncRNA in the M2 polarization of macrophages remains largely unknown.
    Methods: Bioinformatic analysis was used to screen out the differentially expressed lncRNAs in colorectal cancer (CRC). Single-cell RNA sequencing was conducted to investigate the different distribution of cell type in tumor and para-tumor tissues. Function gain and loss assays were performed both in vitro and in vivo to verify the specific role of target genes. The involvement of exosomes was verified by transmission electron microscopy, nano-sight particle tracking analysis and Cre-LoxP system. RNA immunoprecipitation, RNA pull-down, truncation experiment, dual-luciferase reporter assay, chromatin immunoprecipitation, qRT-PCR and Western blot were used to explore the interactions between LINC01615, RBMX and EZH2.
    Results: LINC01615 was highly expressed in CRC and contributed to the M2 polarization of TAMs and progression of CRC. Mechanistically, LINC01615 could be transported from CRC cells to TAMs via exosomes. The exosomal LINC01615 acted as a scaffold to mediate the combination between RBMX and EZH2 mRNA and EZH2 promoter, which promoted EZH2 expression and M2 polarization of TAMs, thus promoting CRC progression.
    Conclusion: Cancer-derived exosomal LINC01615 induces M2 polarization of TAMs via RBMX-EZH2 axis to promote CRC progression, which may be a reliable diagnostic marker and potential therapeutic target for CRC.
    Keywords:  EZH2; LINC01615; RBMX; colorectal cancer; exosome; macrophage
    DOI:  https://doi.org/10.2147/IJN.S499381
  6. Transl Cancer Res. 2025 May 30. 14(5): 3186-3200
    Plasma-derived exosomal human epidermal growth factor receptor 2 (HER2) protein for distinguishing breast cancer from benign breast disease and assessing the efficacy of neoadjuvant therapy.
    Xiaofang Yang, Mengdan Xu, Yu Xia, Zhaofen Ba, Chunmiao Han, Yipu Wang, Jinwen Qu, Yu Wang, Yehui Zhou, Rong Wang, Jing Lan.
       Background: Exosomes derived from liquid biopsy can serve as excellent biomarkers in clinical practices. Human epidermal growth factor receptor 2 (HER2) has been shown to be associated with tumor stage, clinical therapy, and prognosis. However, the clinical value of exosomal HER2 for breast cancer remains unclear. The study aimed to investigate the potential of exosomal HER2 in breast cancer diagnosis, explore its role in guiding clinicians in the selection of treatment options, and find out whether changes in exosomal HER2 levels could be used to evaluate the efficacy of neoadjuvant chemotherapy.
    Methods: The HER2 protein was detected by magnetic particle-based chemiluminescence immunoassay. The study enrolled 51 patients with breast cancer and 36 patients with benign breast disease to evaluate the diagnostic value of exosomal HER2. Additionally, a receiver operating characteristic (ROC) curve was drawn for HER2 immunohistochemistry (IHC) to determine the concordance between exosomal HER2 and HER2 IHC. Furthermore, the exosomal HER2 levels during neoadjuvant therapy were measured to assess the efficacy of neoadjuvant therapy.
    Results: Exosomal HER2 concentration in patients with breast cancer was significantly higher than that in patients with benign breast disease. The optimal cutoff value of exosomal HER2 for diagnosing breast cancer was 772.7 pg/mL, with a sensitivity of 45.1% and a specificity of 97.22%. With 743 pg/mL as the cutoff value, the concordance between exosomal HER2 levels and HER2 IHC was 74.51%, with a sensitivity of 81.25% and a specificity of 71.43%. Exosomal HER2 could be detected in patients receiving neoadjuvant therapy, and some patients (5/8) exhibited a proportional relationship between exosomal HER2 levels and clinical tumor size changes.
    Conclusions: Plasma-derived exosomal HER2 might serve as a promising biomarker for distinguishing breast cancer from benign breast disease, screening patients who could benefit from HER2-targeted therapy, and monitoring neoadjuvant therapy.
    Keywords:  Breast cancer; benign breast disease; exosome; human epidermal growth factor receptor 2 (HER2); neoadjuvant therapy
    DOI:  https://doi.org/10.21037/tcr-2025-825
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