bims-exocan 2026-05-31 papers

Issue of 2026–05–31
five papers selected by
Muhammad Rizwan, COMSATS University

Crit Rev Oncol Hematol. 2026 May 26. pii: S1040-8428(26)00279-9. [Epub ahead of print]224 105392

Exosomes and extracellular vesicles in gastric cancer immune escape.

Pellegrino Mazzone, Carlo Calabrese, Tiziana Notarangelo.

Gastric cancer (GC) remains a major cause of cancer-related mortality, largely due to late-stage diagnosis and the emergence of primary or acquired resistance to standard chemotherapies. Increasing evidence identifies extracellular vesicles (EVs), particularly exosomes, as central mediators of intercellular communication within the tumor microenvironment (TME). Extracellular vesicles (EVs) represent a heterogeneous population of membrane-bound particles that include exosomes, microvesicles, and apoptotic bodies, which differ in size, biogenesis, and functional properties. In this review, the term EVs is used as a comprehensive definition, while exosomes are referred to as a specific subtype originating from the endosomal pathway. Tumor-derived exosomes enriched in proteins, lipids, and nucleic acids profoundly reprogram infiltrating immune cells, shaping a highly immunosuppressive niche that supports tumor progression. In GC, exosomal immune checkpoint ligands, oncogenic non-coding RNAs, and vesicle remodeling driven by Helicobacter pylori infection collectively rewire immune surveillance, fostering a permissive microenvironment that sustains tumor growth and therapeutic resistance. At the clinical level, circulating EVs are emerging as powerful liquid-biopsy tools, supporting early detection, prognostic classification, and the prediction of responses to immune checkpoint inhibitors. Here, we discuss current insights into EV biogenesis and cargo sorting in GC, delineate how EVs reshape anti-tumor immunity and promote immune escape, and explore the translational potential of targeting EVs or their cargos as innovative therapeutic strategies in this aggressive malignancy.

Keywords: Exosomes; Extracellular vesicles; Gastric cancer; Resistance; Tumor microenvironment

DOI: https://doi.org/10.1016/j.critrevonc.2026.105392

Discov Oncol. 2026 May 23.

Exosome-mediated post-transcriptional oncogene regulation as a novel cancer therapeutic strategy.

Bunty Sharma, Kawaljit Singh Kaura, Ranjay Kumar Choudhary, Suresh Babu Kondaveeti, Malathi Hanumanthayya, Abhishek Chauhan, Sanjana Gupta, Himanshu Sharma, Anuj Ranjan, Ambrish Mishra, Ujjawal Sharma.

Exosomes are tiny vesicles (30-150 nm in size) secreted by nearly every cell type that have lately emerged as essential regulators of intercellular communication and gene expression in cancer. They accommodate bioactive cargos such as miRNAs, lncRNAs, circRNAs, and mRNAs, all of which direct oncogene expression at the post-transcriptional level. Exosomal RNAs influence post-transcriptional and epigenetic regulatory mechanisms implicated in tumor activity, including mRNA degradation, translation repression and activation, alternative splicing interference, and epigenetic remodeling, which contribute to tumorigenic processes such as proliferation, angiogenesis, metastasis, immune evasion, and drug resistance. Tumor-derived exosomes also regulate the key oncogenic pathways such as PI3K/AKT, JAK/STAT, and Wnt/β-catenin to promote tumor stroma remodeling, thereby inducing macrophage M2 polarization, fibroblast transformation into cancer-associated fibroblasts, and pre-metastatic niche formation, favoring metastases. Targeting exosome-mediated oncogenic communication has therapeutic potential. Strategies include inhibiting exosome biogenesis and release using GW4869 or blocking Rab GTPases, blocking exosome uptake, and modulating oncogenic RNA cargo using antisense oligonucleotides, RNA interference, or CRISPR/Cas13-mediated RNA editing. Engineered exosomes also serve as natural, biocompatible carriers for the therapeutic delivery of siRNAs, miRNA mimics, mRNAs, or CRISPR components, offering improved stability, specificity, and reduced immunogenicity compared to synthetic counterparts. There are significant translational challenges, including large-scale manufacturing, purification, standardization, and biosafety testing, despite promising preclinical and early clinical results. In summary, comprehending and implementing post-transcriptional oncogene regulation via exosomes is a transformative strategy in precision oncology, creating new opportunities in targeted diagnosis, prognostication, and advanced cancer therapies.

Keywords: Exosomes; Oncogene modulation; Post-transcriptional regulation; Tumor microenvironment; lncRNA; miRNA

DOI: https://doi.org/10.1007/s12672-026-05255-y

Biomolecules. 2026 May 05. pii: 682. [Epub ahead of print]16(5):

Exosomal MicroRNAs as Drivers of Desmoplasia and Treatment Resistance in Breast Cancer: Mechanisms, Biomarker Potential, and Therapeutic Opportunities.

Jun Chung, Young Hwa Soung.

Exosomal microRNAs (miRNAs) are key mediators of intercellular communication in the breast cancer tumor microenvironment (TME), facilitating bidirectional signaling between malignant cells and the desmoplastic stroma. This review explores current evidence on their dual roles as drivers of stromal remodeling and as circulating biomarkers of therapeutic resistance across major breast cancer subtypes, including triple-negative breast cancer (TNBC), hormone receptor-positive (ER+/PR+) disease, and HER2-amplified tumors. We outline how miR-9, miR-21, and miR-181 family members promote cancer-associated fibroblast (CAF) activation, increase extracellular matrix (ECM) stiffness, and sustain a reverse Warburg phenotype. We then detail subtype-specific resistance mechanisms: miR-181 family members suppress BCLAF1 to block doxorubicin-induced apoptosis; miR-221/222 downregulates ESR1 and p27Kip1 to confer tamoxifen resistance; miR-155 impairs homologous recombination in TNBC; and miR-1246 sustains PI3K/AKT signaling in HER2-positive disease. We also evaluate circulating exosomal miRNA panels as liquid biopsy tools for predicting chemotherapy response and tracking resistance emergence. Finally, we discuss therapeutic strategies including antagomirs, miRNA replacement therapy and engineered exosome platforms, and address key challenges such as assay standardization and regulatory hurdles, that must be overcome for clinical translation.

Keywords: breast cancer; cancer-associated fibroblasts; chemoresistance; desmoplasia; endocrine resistance; exosomes; liquid biopsy; mechanotransduction; miR-181 family; microRNA; triple-negative breast cancer; tumor microenvironment

DOI: https://doi.org/10.3390/biom16050682

Clin Chim Acta. 2026 May 23. pii: S0009-8981(26)00280-9. [Epub ahead of print]591 121098

Harnessing extracellular vesicles for gastric cancer management: Biomarker discovery and therapeutic strategies.

Ghaleb Oriquat, Ahmed Faisal Mutee, Aziz Kubaev, Zarina Tillyayeva, Rasim M Salih, Mohamed Adil Jaber, Safa Hussen.

Extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication in gastric cancer (GC), functioning as both pathogenic drivers and promising therapeutic tools. Tumor-derived EVs (TEVs) actively remodel the tumor microenvironment by promoting immune evasion, metastasis, angiogenesis, and therapy resistance, largely through the transfer of oncogenic proteins and non-coding RNAs such as miR-21 and circSMARCC1. In contrast, EVs from mesenchymal stromal cells and immune cells offer opportunities for innovative therapeutic strategies, including targeted drug delivery, immune modulation, and gene-silencing approaches such as anti-PD-L1 small interfering RNA (siRNA) delivery. EVs also hold substantial promise as non-invasive biomarkers, with exosomal ncRNAs, proteins, and DNA methylation signatures demonstrating superior diagnostic and prognostic performance compared to traditional serum markers. Despite these advances, challenges persist in standardizing EV isolation, scaling manufacturing, ensuring quality control, and navigating regulatory pathways. This narrative review synthesizes current insights into the dualistic roles of EVs in GC pathogenesis, diagnostics, and therapeutics, highlighting their transformative potential while underscoring the critical barriers that must be addressed to enable clinical translation. As EV-based technologies evolve, they offer a compelling foundation for precision oncology and integrated theranostic strategies in gastric cancer management.

Keywords: Biomarkers; Extracellular vesicles; Gastric cancer; Nanomedicine

DOI: https://doi.org/10.1016/j.cca.2026.121098

Discov Oncol. 2026 May 24.

A prognostic exosome-related mRNAs risk signature correlates with the immune microenvironment in breast cancer.

Duntao Su, Bida Peng, Wei Peng, Ning Bai, Zhaochangci Chen.

BACKGROUND: Breast cancer (BC) represents one of the most prevalent malignancies among women worldwide. Despite substantial advances in diagnostic and therapeutic modalities and pharmacological interventions in recent years, the accurate assessment of prognosis continues to pose formidable challenges. Exosomes exert pivotal roles in tumorigenesis, tumor progression, and immune modulation, with exosome-related mRNAs emerging as promising novel prognostic biomarkers. Nevertheless, the role of exosome-related mRNA in BC oncogenesis, progression, and prognostic prediction warrants further extensive investigation.
METHODS: The study constructed the exosome-related signature and validated the results in the Gene Expression Omnibus database (GSE9893). Candidate genes were selected based on differential expression, univariate Cox, and LASSO regression to build a prognostic risk model. Its predictive accuracy was evaluated using Kaplan-Meier (K-M) survival curves and time-dependent ROC analysis. Furthermore, the ESTIMATE and CIBERSORT algorithms were employed to elucidate the association between the prognostic risk signature and tumor immune microenvironment (TIME), alongside comparative analyses of HLA gene and immune checkpoint expression differences. GSEA was subsequently conducted to explore the potential biological pathways associated with the prognostic risk signature and individual signature genes. In addition, qRT-PCR was performed in breast cancer cell lines to experimentally validate the expression of signature genes. Finally, a nomogram was developed by combining risk scores with clinical features.
RESULTS: Ultimately, four exosome-related mRNAs were identified to construct a prognostic risk signature. In the TCGA cohort, this signature effectively stratified patients into high- and low-risk groups with respect to overall survival (OS), as evidenced by robust predictive performance in ROC analysis. In the GEO validation cohort (GSE9893), results aligned with the training cohor. Immunological analyses showed the risk score's association with the tumor microenvironment (TME), encompassing stromal scores, immune cell abundance, and HLA gene and immune checkpoint levels. In vitro qRT-PCR validation demonstrated expression trends consistent with the computational predictions. The nomogram integrating clinical characteristics demonstrated calibration and substantial clinical utility.
CONCLUSION: This study innovatively developed a BC prognostic risk signature based on exosome-related mRNAs, which not only effectively predicts patient survival but also elucidates its intimate association with the TIME. This signature offers novel insights and substantial clinical utility for personalized prognostic evaluation and treatment decision-making in BC patients.

Keywords: Breast cancer; Exosome-related mRNA; Prognostic signature; Tumor immune microenvironment

DOI: https://doi.org/10.1007/s12672-026-05261-0