bims-exocan 2026-01-25 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2026–01–25
seven papers selected by
Muhammad Rizwan, COMSATS University

Emerging clinical applications of exosomes in breast cancer management from biomarkers to therapeutics.
Exosomal crosstalk: the metastatic language of hepatocellular carcinoma.
Engineering exosomes for cancer therapy - Modification technologies and subcellular targeting strategies: A review.
The Role of MSC-Derived Exosomes in Immune Modulation and Regenerative Medicine.
Extracellular vesicles in malignant and normal B lymphocyte growth and development.
Activated hepatic stellate cell-derived exosomal miR-23a-3p promotes hepatocellular carcinogenesis by regulating DUSP5/ERK signaling.
Extracellular vesicle-associated lncRNA LYPLAL1-DT mediates endothelial-cancer cell communication, promoting small cell lung cancer progression.

Discov Oncol. 2026 Jan 21.

Emerging clinical applications of exosomes in breast cancer management from biomarkers to therapeutics.

Xiangmei Wu, Wenjing Wang.

  Exosomes, nano-sized extracellular vesicles carrying distinct molecular cargoes inherited from their parent cells, have emerged as critical mediators of intercellular communication in cancer. In breast cancer, tumor-derived exosomes (TDEs) possess unique molecular signatures and demonstrate remarkable potential in reshaping the tumor microenvironment, modulating immune responses, and driving disease progression. Growing evidence supports the diagnostic utility of TDEs in early detection and molecular subtyping of breast cancer, particularly via non-invasive liquid biopsy approaches. Meanwhile, exosomes in the breast cancer tumor microenvironment mediate intercellular communication and transmit pro-tumorigenic signals among various cell populations, thereby playing a pivotal role in promoting cell proliferation, angiogenesis, and tumor metastasis. On the therapeutic front, two strategies are attracting growing attention: inhibition of exosome biogenesis or reduction of circulating TDEs to disrupt tumor communication, and the engineering of exosomes as targeted delivery systems for drugs, RNAs, or immune modulators. Collectively, this review summarizes the current understanding of exosome biology in breast cancer and highlights the translational potential of both native and engineered exosomes as diagnostic and therapeutic tools. Continued research into exosome mechanisms and technologies will undoubtedly accelerate their integration into precision oncology.

Keywords:  Breast cancer; Engineered exosomes; Exosomes; Liquid biopsy; Tumor microenvironment

DOI:  https://doi.org/10.1007/s12672-026-04417-2
Front Immunol. 2025 ;16 1701305

Exosomal crosstalk: the metastatic language of hepatocellular carcinoma.

Qian Xu, Jinhan Chen, Yi Liu, Jinsheng Yu, Fangmin Zhao, Qijin Shu.

  Exosomes have garnered considerable attention in hepatocellular carcinoma (HCC) research owing to their critical function in regulating intercellular communication within the tumor microenvironment. Their inherent composition, structural integrity, and cargo-specific properties underpin critical functions in orchestrating cellular information transfer. This review delineates the fundamental biology of exosomes, their multifaceted pathophysiological roles in HCC, and the inherent translational promise of exosome-based therapeutic platforms for HCC management. Emerging evidence positions exosomes as dual-functional entities in HCC: not only propagating tumor progression and metastasis but also emerging as liquid biopsy-based diagnostic indicators for early detection and prognostic stratification, as well as nanoscale delivery platforms for site-specific therapeutic payloads. Nevertheless, despite growing recognition of exosomal functions in HCC, the precise mechanisms governing their functional duality and clinical translatability demand further elucidation. Through critical appraisal of extant literature, this review delineates actionable research priorities to catalyze mechanistic dissection and accelerate bench-to-bedside translation in exosome-based HCC management.

Keywords:  biomarkers; exosomes; hepatocellular carcinoma; intercellular communication; therapeutic targets

DOI:  https://doi.org/10.3389/fimmu.2025.1701305
Int J Pharm X. 2026 Jun;11 100473

Engineering exosomes for cancer therapy - Modification technologies and subcellular targeting strategies: A review.

Fengbo Liu, Chengxing Xia, Hang Yu, Xiaofang Yang, Liping Ge, Chunwei Ye.

  Exosomes are secreted lipid bilayer vesicles of 30-150 nm in diameter. Their low immunogenicity, excellent biocompatibility, and inherent targeting capability make them a promising drug delivery vehicle for cancer therapeutics. However, the use of natural exosomes is still challenging for therapeutic applications, including limited targeting precision and drug-loading efficiency, necessitating engineered modification strategies to optimize their performance. To further enhance exosome targeting capacity, recent studies have explored precision delivery strategies targeting subcellular structures such as lysosomes, nuclei, mitochondria, and the endoplasmic reticulum, thereby improving exosome therapeutic potential. This review systematically summarizes the core advantages of exosomes as drug carriers, elaborates on their engineering modification methods, and highlights recent advances in strategies to improve exosomes targeting of subcellular structures to enhance antitumor efficacy. The review aims to provide a theoretical foundation and technical guidance for developing exosome-based precision therapies for cancer.

Keywords:  Cancer; Exosome; Modification; Subcellular targeting; Therapy

DOI:  https://doi.org/10.1016/j.ijpx.2025.100473
J Drug Target. 2026 Jan 22. 1-35

The Role of MSC-Derived Exosomes in Immune Modulation and Regenerative Medicine.

Surya Nath Pandey, Muhammad Afzal, Kavita Goyal, Rekha M M, Priya Priyadarshini Nayak, Mudasir Maqbool, Yumna Khan, Chandana Maji, Gaurav Gupta, Sami I Alzarea, Imran Kazmi, Md Sadique Hussain.

  Mesenchymal stem cells (MSC)-derived exosomes have been identified as highly potential, cell-free therapeutic agents that play pivotal roles in immune-based modulation in conjunction with regenerative medicine. These extracellular vesicles are mostly isolated using ultracentrifugation, size-exclusion chromatography, or immunoaffinity capture and carry a wide range of bioactive molecules (lipids, nucleic acids, and proteins). MSC-derived exosomes have strong immunomodulatory properties, such as inhibition of pro-inflammatory cytokines, expansion of regulatory T cells, and induction of an anti-inflammatory microenvironment. Therapeutically, they are influential in various disease models, some of which include autoimmune disorders, cardiovascular disease, etc. Engineered MSC-derived exosomes present an exciting potential as a drug delivery vehicle in the field of oncology as a means of addressing chemoresistance and improving drug bioavailability. Exosomes have several advantages over MSC-based therapies. Distinct from previous reviews that have examined immunomodulation or regenerative indications in isolation, this article specifically integrates cargo-defined immune rewiring by MSC-derived exosomes with organ-specific regenerative outcomes across inflammatory, autoimmune, oncologic, and neurodegenerative disorders, and links these mechanisms to emerging drug-sensitization strategies and early-phase clinical trials. This narrative review includes the strategies of purifying MSC-derived exosomes and their potential therapeutic importance in diseases, where standardized methods are needed to improve clinical translation.

Keywords:  Drug Delivery; Exosome Therapy; Immune Regulation; Immunomodulation; Regenerative Medicine; Tissue Repair

DOI:  https://doi.org/10.1080/1061186X.2026.2620707
Extracell Vesicles Circ Nucl Acids. 2025 ;6(4): 937-953

Extracellular vesicles in malignant and normal B lymphocyte growth and development.

Kaitlyn E Mayne, Rashid Jafardoust, Hong-Dien Phan, Sherri L Christian.

  Extracellular vesicles (EVs) are central mediators of intercellular communication in both healthy and malignant states. In normal B lymphocyte (cell) biology, EVs derived from B cells, mast cells, T cells, and mesenchymal stromal cells regulate maturation, antigen presentation, and activation. B cell-derived EVs can either suppress excessive activation to maintain immune homeostasis or amplify responses during an active immune response. Modulation of these responses often occurs via phosphoinositide 3-kinase signaling pathways in recipient cells. In B cell malignancies, such as leukemias, lymphomas, and multiple myeloma, EVs play pivotal roles in disease progression and therapy resistance. Tumor- and stromal-derived EVs can transfer pro-survival proteins, regulatory RNAs, and drug-resistance factors to directly promote tumor progression. In addition, EVs can shape the tumor microenvironment to indirectly promote tumor progression through macrophage polarization, stromal cell reprogramming, and suppression of anti-tumor immunity. Conversely, under certain conditions, B cell EVs can enhance immune surveillance by stimulating T cells and presenting antigen, highlighting their dual potential in cancer biology. Clinically, B cell-derived EVs represent promising liquid biopsy biomarkers: increases in EV abundance, expression of surface antigens, altered protein cargo, and distinct RNA signatures have been associated with disease stage, treatment response, and patient outcomes. Despite this potential, variability in EV isolation and analysis methods remains a barrier to clinical translation. Moving forward, identifying robust biomarker signatures across platforms and clarifying mechanisms of cargo selection and EV uptake will be critical for advancing diagnostic and therapeutic applications. Overall, B cell-derived EVs act as contextual regulators of immune function and malignancy, positioning them as both modulators of disease progression and promising clinical tools.

Keywords:  B lymphocyte; Extracellular vesicles; cancer development; microenvironment; normal development

DOI:  https://doi.org/10.20517/evcna.2025.42
J Adv Res. 2026 Jan 17. pii: S2090-1232(26)00063-9. [Epub ahead of print]

Activated hepatic stellate cell-derived exosomal miR-23a-3p promotes hepatocellular carcinogenesis by regulating DUSP5/ERK signaling.

Xiaona Lu, Jia Shi, Wenlan Zheng, Shihan Yu, Xuemei Zhang, Hai Feng, Yueqiu Gao, Zhuo Yu.

   INTRODUCTION: Activation of hepatic stellate cells (HSCs) is a core driver of liver fibrosis and may contribute to the evolution to hepatocellular carcinoma (HCC). Exosomes mediate intercellular signaling by transporting bioactive molecules, yet the role of activated HSC-derived exosomes in hepatocarcinogenesis remains unexplored.
OBJECTIVES: This study aims to investigate whether and how activated HSCs induce hepatocarcinogenesis through the mediation of exosomes.
METHODS: Exosomes from activated HSCs were isolated and applied to hepatocytes to assess malignant transformation via immunoblotting, soft-agar colony formation, and xenograft assays. Oncogenic miRNAs were screened by sequencing and validated by qPCR. Target genes and signaling pathways were identified through transcriptomics, bioinformatics, and dual-luciferase assays. Functional roles of miRNAs and downstream pathways were confirmed via gain/loss-of-function experiments. Clinical correlations and diagnostic potential of exosomal miRNAs were evaluated using patient samples.
RESULTS: Exosomes from activated HSCs induced hepatocyte malignant transformation in vitro and tumorigenesis in vivo. MiR-23a-3p was markedly enriched in activated HSC-derived exosomes and exerted oncogenic effect upon delivery to recipient hepatocytes. Mechanistically, exosomal miR-23a-3p directly targeted DUSP5 in hepatocytes, thereby suppressing its expression and subsequently activating pro-oncogenic ERK signaling. Notably, the miR-23a-3p/DUSP5/ERK signaling axis exhibited progressive activation that paralleled histopathological transitions from fibrosis to HCC in both murine models and clinical specimens. Clinically, elevated plasma exosomal miR-23a-3p levels demonstrated significant diagnostic merit for detecting precancerous lesions and predicting HCC onset in patient cohorts.
CONCLUSION: Our results indicate that activated HSCs secrete exosomes enriched with miR-23a-3p, which directly target to inhibit DUSP5, and subsequently activate ERK signaling in hepatocytes, leading to the initiation of cellular malignant transformation and tumorigenesis.

Keywords:  Activated hepatic stellate cells; DUSP5; ERK signaling; Exosome; Hepatocarcinoma.; MiR-23a-3p

DOI:  https://doi.org/10.1016/j.jare.2026.01.038
Extracell Vesicles Circ Nucl Acids. 2025 ;6(4): 1015-1033

Extracellular vesicle-associated lncRNA LYPLAL1-DT mediates endothelial-cancer cell communication, promoting small cell lung cancer progression.

Xing Zhang, Caijiao Hu, Zhihui Li, Jing Lu, Xueyun Huo, Lixue Cao, Meng Guo, Changlong Li, Xin Liu, Zhenwen Chen, Jianyi Lv, Xiaoyan Du.

  Aim: Representing about 15% of lung cancers, small cell lung cancer (SCLC) is an extremely aggressive disease characterized by rapid growth and early spread, leading to dismal clinical outcomes. In this study, we aimed to investigate the dual roles of exosomal long non-coding RNA (lncRNA) LYPLAL1-DT (LYPLAL1 divergent transcript) in both tumor cells and vascular endothelial cells. Methods: The circulating levels of LYPLAL1-DT were measured using real-time polymerase chain reaction in 13 SCLC patients and 21 normal controls. Exosomes from the supernatant of cell culture medium or serum were extracted through ultracentrifugation and dyed with PKH67 green fluorescent cell linker to identify internalization. Migration and invasion assay, colony formation, Cell Counting Kit-8 (CCK-8), and tube formation assays were used to assess the malignant effects of extracellular RNAs (exRNAs) LYPLAL1-DT in exosomes. Results: Exosomal LYPLAL1-DT is upregulated in SCLC patients and plays a dual role in promoting tumor cell aggressiveness and enhancing pro-angiogenic behavior in endothelial cells, thereby accelerating SCLC progression. Mechanistically, LYPLAL1-DT functions as a competing endogenous RNA, exerting its effects through the miR-204-5p/profilin-2, miR-204-5p/B-cell lymphoma 2 and miR-204-5p/sirtuin 1 regulatory axes. These pathways underscore the pleiotropic effects of exosomal LYPLAL1-DT and underscore its value as a promising therapeutic target. Conclusion: In the current study, we investigated the bidirectional communication mediated by exRNA LYPLAL1-DT between SCLC and endothelial cells, while also exploring its potential regulatory targets. This research provides a potential circulating biomarker for the diagnosis, prognosis, and treatment of SCLC.

Keywords:  BCL2; LYPLAL1-DT; PFN2; SCLC; SIRT1; endothelial cells; exosome

DOI:  https://doi.org/10.20517/evcna.2025.119