bims-exocan 2026-04-19 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2026–04–19
six papers selected by
Muhammad Rizwan, COMSATS University

Extracellular Vesicles in Pancreatic Cancer Function and Potential Clinical Applications.
Diagnostic and Therapeutic Applications of Exosomes in Lung Cancer.
Engineering Extracellular Vesicles for Tumor Targeted Therapy: Source Optimization, Modification, and Clinical Application.
Plasma-derived exosomal miRNA as a promising diagnostic biomarker for detection of diffuse large B-cell lymphoma.
mTOR-driven integrin β4-enriched extracellular vesicles from lenvatinib-resistant hepatocellular carcinoma fuel lung metastasis via fibroblast-niche formation.
Tumor-targeted Exosomal Delivery of Celastrol for Enhanced Therapeutic Efficacy in NSCLC.

Onco Targets Ther. 2026 ;19 591622

Extracellular Vesicles in Pancreatic Cancer Function and Potential Clinical Applications.

Dai Li, Jian-Jun Fang, Zhi-Long Jiang.

  Pancreatic cancer (PC) is one of the most aggressive gastrointestinal malignancies, characterized by a dismal 5-year survival rate. This poor prognosis is primarily attributed to delayed early detection, rapid disease progression, surgical complexities, and the limited efficacy of conventional oncological therapies. Extracellular vesicles (EVs) are nanoscale, cell-secreted vesicles that transport bioactive cargoes, including nucleic acids, proteins, and lipids. Upon release into the extracellular space, EVs facilitate short and long-distance intercellular communication and molecular transport via multiple pathways. In this review, we elucidate the multifaceted roles of EVs within the highly malignant PC microenvironment, specifically focusing on their mediation of intricate crosstalk between tumor and stromal cells. Furthermore, we summarize potential EV-based biomarkers for PC diagnosis and the recent advances in leveraging EVs as therapeutic platforms across radiotherapy, gene therapy, and immunotherapy. Ultimately, this review aims to provide novel insights into the clinical management of PC to improve patient outcomes and quality of life.

Keywords:  diagnosis; drug delivery; extracellular vesicles; nanomedicine; pancreatic cancer

DOI:  https://doi.org/10.2147/OTT.S591622
Cells. 2026 Mar 31. pii: 632. [Epub ahead of print]15(7):

Diagnostic and Therapeutic Applications of Exosomes in Lung Cancer.

Disha Nagesh Moholkar, Raghuram Kandimalla, Margaret Wallen, Kavitha Yaddanapudi, Ramesh Gupta, Farrukh Aqil.

  Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with a five-year survival rate of only 26%, primarily due to late-stage diagnosis and limited treatment options. Exosomes, nanosized extracellular vesicles released by nearly all cell types, have emerged as promising tools in both diagnostics and therapeutics. Their unique composition containing proteins, lipids, and nucleic acids reflects the molecular profile of their cell of origin, making them excellent candidates for non-invasive early detection biomarkers. For therapeutic applications, exosomes offer biocompatible, low-immunogenicity platforms capable of delivering diverse therapeutic agents, including small molecules, siRNAs, and antimetabolites, directly to tumor cells while minimizing systemic toxicity. Functionalization strategies, such as folic acid tagging, have further enhanced tumor specificity, especially in cancers with high folate receptors. However, clinical translation is hindered by challenges including lack of standardized isolation and characterization methods, high production costs, and regulatory uncertainties. Despite these limitations, ongoing research continues to optimize exosome production, targeting, and integration with conventional therapies. Milk- and colostrum-derived exosomes have shown promising potential due to their abundance, scalability, oral bioavailability, and safety. Collectively, exosomes represent a transformative approach in lung cancer management, with the potential to improve early diagnosis, enhance therapeutic efficacy, and reduce adverse effects, thereby offering a path toward more personalized and effective cancer care.

Keywords:  clinical applications; diagnostics; exosomes; lung cancer; targeted therapy

DOI:  https://doi.org/10.3390/cells15070632
Int J Nanomedicine. 2026 ;21 592579

Engineering Extracellular Vesicles for Tumor Targeted Therapy: Source Optimization, Modification, and Clinical Application.

Jiaxin Sui, HanBin Qin, Zile Zhang, Xiaojing Lv, Xinhua Lin, Zhonglu Liu, Xin Zhao, Xuexia Liu, Hua Zhang.

  Cancer remains a leading cause of global morbidity and mortality, yet conventional therapies, including surgery, radiotherapy, and chemotherapy, are often limited by invasiveness, systemic toxicity, and drug resistance. In this context, extracellular vesicles (EVs) have emerged as a promising cell-free nanotherapeutic platform. As endogenous nanocarriers, EVs enable precise, targeted delivery of diverse bioactive cargoes (eg, nucleic acids, chemotherapeutics, immunomodulators) to tumor tissues, thereby enhancing therapeutic efficacy while minimizing off-target effects, which is the key advantages for their application in tumor targeted therapy. This review systematically summarizes the characteristics of animal-derived and plant-derived EVs and highlights their translational applications in multiple cancers via immune activation, targeted delivery, tumor microenvironment remodeling, and anti-angiogenesis. We further introduce advanced bioengineering strategies for EV modification to optimize cargo loading, targeting specificity, and in vivo stability, particularly frontier innovations such as artificial intelligence-assisted design and microfluidic manufacturing that improve the precision, controllability, and scalability of engineered EVs. Compared to synthetic nanocarriers, EVs exhibit unique advantages, including excellent biocompatibility, low immunogenicity, and superior ability to cross biological barriers. However, the clinical application of EV-based therapies faces notable challenges, including EV heterogeneity, scalability of production, standardization of characterization methods, cargo loading efficiency, and long-term safety concerns. This review emphasizes the transformative potential of engineered EVs in advancing tumor targeted therapy and improving outcomes for patients with refractory or metastatic tumors.

Keywords:  EVs; clinical translation; engineered EVs; extracellular vesicles; tumor microenvironment; tumor targeted therapy

DOI:  https://doi.org/10.2147/IJN.S592579
Transl Cancer Res. 2026 Mar 31. 15(3): 141

Plasma-derived exosomal miRNA as a promising diagnostic biomarker for detection of diffuse large B-cell lymphoma.

Yunfei Zhao, Anna Su, Gulimire Adili, Laxin Sabitjan, Xun Li.

   Background: Diffuse large B-cell lymphoma (DLBCL) is a malignant tumor with moderate-high aggressiveness and heterogeneity. In recent years, several studies have shown that tumor cell-derived exosomes are involved in the process of tumorigenesis and progression through microRNA (miRNA). Therefore, exosomal miRNAs are potential diagnostic and prognostic biomarkers for cancer. The aim of this study was to explore the potential of a set of exosomal miRNAs in peripheral blood as noninvasive biomarkers for the auxiliary diagnosis of DLBCL.
Methods: Exosomes were collected from the peripheral blood of three DLBCL patients and two healthy controls, and miRNA expression was detected using high-throughput sequencing technology. MiRNAs were analyzed by Weighted Gene Co-expression Network Analysis to screen out the correlated model genes of DLBCL, subsequently, receiver operating characteristic (ROC) curves were constructed to verify the diagnostic efficacy of this group of miRNAs and validation was performed using the GSE171272 dataset. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the target genes of hsa-miR-589-5p, hsa-miR-4728-3p and hsa-miR-5006-3p.
Results: We identified eight exosomal miRNAs with the potential to differentiate DLBCL patients from healthy controls. ROC curves were generated using the GSE171272 dataset to assess the diagnostic performance of these miRNAs. Among them, hsa-miR-589-5p, hsa-miR-4728-3p, hsa-miR-5006-3p, hsa-miR-30b-5p, hsa-miR-4323, hsa-miR-484, hsa-miR-4500, and hsa-miR-99a-5p exhibited an AUC greater than 0.8. Specifically, the area under the curve (AUC) of hsa-miR-589-5p, hsa-miR-4728-3p and hsa-miR-5006-3p were both 1.00 [95% confidence interval (CI): 0.93-1.00].
Conclusions: In this study, exosomal miRNAs contribute to the diagnosis of DLBCL and may serve as non-invasive diagnostic biomarkers for DLBCL. This offers novel perspectives on utilizing exosomal miRNAs for the early identification of DLBCL and their potential clinical application. However, given the small size of the discovery cohort, these estimates are presented as exploratory and should be confirmed in larger independent cohorts.

Keywords:  Diffuse large B-cell lymphoma (DLBCL); diagnostic biomarkers; exosomes; microRNA (miRNA)

DOI:  https://doi.org/10.21037/tcr-2025-1296
Signal Transduct Target Ther. 2026 Apr 16. pii: 138. [Epub ahead of print]11(1):

mTOR-driven integrin β4-enriched extracellular vesicles from lenvatinib-resistant hepatocellular carcinoma fuel lung metastasis via fibroblast-niche formation.

Tiantian Zou, Xufeng Wang, Haoting Sun, Beiyuan Hu, Jianhua Li, Yu Guo, Zilu Tian, Hao Xu, Yan Zheng, Yinghan Su, Chak Lam Chan, Le Zhu, Keyu Shen, Xiaotian Shen, Qiongzhu Dong, Lun-Xiu Qin.

Tumor-derived extracellular vesicles (EVs) play crucial roles in facilitating the colonization and growth of metastatic cancer cells in distant organs. Nevertheless, the precise mechanisms by which EVs contribute to therapy-resistant cancer dissemination remain poorly understood. In the present study, we aim to investigate how EVs derived from lenvatinib-resistant (LR) hepatocellular carcinoma (HCC) drive lung metastasis and identify potential therapeutic targets for both inhibiting metastasis and overcoming lenvatinib resistance. Using LR HCC models and omics analysis, we demonstrated that LR HCC cells exhibited an enhanced metastatic potential towards the lungs owing to an increased release of EVs. Aberrant activation of mTOR signaling drove EVs secretion from LR cells by impeding the autophagic degradation of multivesicular bodies (MVBs). Furthermore, EVs derived from LR cells exhibited an enrichment of ITGβ4, thereby fostering the pre-metastatic niche (PMN) formation by activating lung fibroblasts via the ITGβ4-laminin interaction and the PI3K-AKT-p65 signaling pathway. Elevated levels of plasma EV-ITGβ4 were observed in LR HCC patients and associated with dismal prognosis. Moreover, inhibition of mTOR signaling using rapamycin impeded lung metastasis and restored the sensitivity to lenvatinib. These findings highlight the role of ITGβ4-enriched EVs released from LR HCC cells in promoting lung metastasis and propose a potential target for combating lung metastasis and overcoming lenvatinib resistance.

DOI: https://doi.org/10.1038/s41392-026-02625-4
Theranostics. 2026 ;16(10): 5125-5149

Tumor-targeted Exosomal Delivery of Celastrol for Enhanced Therapeutic Efficacy in NSCLC.

Disha Nagesh Moholkar, Raghuram Kandimalla, Mohd Saeed, Yaseera Arif, Neha Tyagi, Richa Singhal, Al-Hassan Kyakulaga, Amir Saeed, Margaret Wallen, Ramesh Gupta, Farrukh Aqil.

   Rationale: Non-small cell lung cancer (NSCLC) continues to impose a significant global mortality burden, due to limited therapies, drug resistance, and treatment-related toxicity. Exosomes offer promise for the targeted delivery of therapeutic agents.
Methods: Exosomes were isolated from bovine colostrum and characterized for size, polydispersity index, and surface charge. Celastrol (CEL) was loaded onto exosomes (ExoCEL), and Folic Acid (FA)-functionalized exosomes (FA-ExoCEL) and validated using fluorescence quenching and protease sensitivity assay. Anticancer activity was assessed in NSCLC cell lines using colony formation, cell migration and uptake assays. Transcriptomic (RNA-seq) and protein analysis were performed to analyze gene expression changes. Biodistribution, oral uptake and potential toxicity were evaluated in wild-type mice, while oral antitumor efficacy was tested in orthotopic lung tumor models comparing CEL, ExoCEL and FA-ExoCEL. Synergistic activity with paclitaxel was assessed in chemoresistant cells.
Results: Exosomes were isolated, characterized and efficiently loaded with CEL. ExoCEL demonstrated superior antiproliferative effects in NSCLC cell lines and enhanced potency in drug-resistant A549TR cells compared to free CEL. ExoCEL significantly inhibited colony formation and cell migration in a dose-dependent manner. RNA Seq and protein analyses showed that CEL and ExoCEL reversed TGF-β-induced EMT, restored epithelial markers, suppressed mesenchymal, oncogenic and extracellular matrix related markers. In orthotopic lung tumor models, FA-ExoCEL achieved approximately 80-90% tumor inhibition, outperforming both free CEL and ExoCEL. Oral delivery of FA-ExoCEL resulted in efficient gastrointestinal uptake, selective tumor targeting, recovery of exosomal markers in circulation and no observed systemic toxicity. CEL exhibited strong synergy with paclitaxel, with exosomal delivery further enhancing paclitaxel efficacy in resistant cells.
Conclusions: FA-ExoCEL represents a safe, scalable, and effective oral therapeutic strategy for NSCLC. By combining exosome-mediated delivery with folate-targeted tumor accumulation, this platform enhances CEL bioavailability, and improves antitumor efficacy, supporting its translational potential for lung cancer therapy.

Keywords:  Celastrol; Chemoresistance; Epithelial-to-mesenchymal transition (EMT); Exosomes; Lung cancer.; Oral targeted delivery

DOI:  https://doi.org/10.7150/thno.125096