bims-exocan 2026-07-26 papers

Issue of 2026–07–26
three papers selected by
Muhammad Rizwan, COMSATS University

Cancer Cell Int. 2026 Jul 20.

Exosomes in cancer drug resistance: dual roles in therapy failure and emerging precision therapeutics.

Bantayehu Addis Tegegne, Habtamu Belew, Zigale Hibstu Teffera, Mekuriaw Belayneh, Desalegn Abebaw, Misganaw Fikrie, Mohammed Jemal, Temesgen Baylie, Fasil Tadesse, Samuel Agegnew Wondm, Tirsit Ketsela Zeleke, Wubetu Yihunie Belay.

Exosomes play a key role in cancer, functioning both as drivers of drug resistance and as tools for therapy. Tumor-derived exosomes facilitate intercellular communication through selective transfer of bioactive cargo, including proteins (e.g., P-gp, PD-L1), nucleic acids (e.g., miR-21, lncRNA H19), lipids, and metabolites. These cargos remodel the tumor microenvironment, activate oncogenic pathways such as PI3K/AKT and MAPK, and promote drug resistance, immune evasion, and metabolic reprogramming. This work presents a conceptually integrated translational perspective, introducing the 'exosome paradox' to unify the dual roles of exosomes in therapy resistance and therapeutic application. The review incorporates cancer-specific insights, highlighting how resistance mechanisms vary across pancreatic, breast, lung, colorectal, and ovarian cancers, underscoring the need for context-dependent strategies. Mechanistically, we integrate emerging advances in exosome heterogeneity, selective cargo loading (including SUMOylation-dependent pathways), and the metabolic-epigenetic interface, particularly the lactate-lactylation axis. We also explore the growing role of artificial intelligence in biomarker discovery, cargo profiling, and rational design of engineered exosomes. Therapeutically, two complementary strategies are emphasized: inhibition of pathogenic exosome biogenesis, secretion, and uptake, and development of engineered exosomes as delivery vehicles for chemotherapeutics, RNA-based therapies, and CRISPR/Cas9 systems. Despite promising preclinical advances, clinical translation remains limited by challenges in targeting specificity, pharmacokinetics, scalable manufacturing, and regulatory standardization. This review provides a unified framework combining suppression of pathogenic exosome signaling with strategic engineering of therapeutic exosomes, offering new directions for overcoming drug resistance and advancing precision oncology.

Keywords: Artificial intelligence in oncology; Cancer drug resistance; Exosome paradox; Exosome-based therapeutics; Precision oncology; Tumor-derived exosomes

DOI: https://doi.org/10.1186/s12935-026-04396-y

Mamm Genome. 2026 Jul 18. pii: 90. [Epub ahead of print]37(1):

Hypoxia-induced mechanism of TNBC promoting tumour cell proliferation through exosomal miRNA.

Xiangxin Zheng, Peng Yang, Sai Zhou, Xiaochao Zhu, Xiaoqing Guan, Guoqin Jiang.

Triple-negative breast cancer (TNBC), characterized by the absence of ER, PR, and HER2 expression, is associated with aggressive clinical behavior and limited treatment options. Hypoxia in the tumor microenvironment (TME) may influence intercellular communication through exosomes. In this study, we investigated whether hypoxia-derived exosomes regulate malignant phenotypes of TNBC cells through exosomal miRNAs. Exosomes derived from hypoxic TNBC cells increased proliferation, migration, and invasion of recipient TNBC cells compared with normoxia-derived exosomes. Small RNA sequencing and RT-qPCR validation showed enrichment of miR-4791 in hypoxia-derived exosomes. Functional assays indicated that miR-4791 overexpression promoted TNBC cell proliferation, whereas miR-4791 inhibition reduced proliferative capacity. Mechanistically, miR-4791 directly targeted the 3'UTR of CTCFL and was associated with reduced PTEN expression. Rescue experiments suggested that restoration of CTCFL or PTEN partially attenuated miR-4791-associated malignant phenotypes in vitro and in vivo. Analysis of GSE19536 showed higher miR-4791 expression in breast cancer tissues than in normal tissues; however, the number of normal samples was limited. Survival analysis using GSE19783 indicated that higher miR-4791 expression was associated with poorer survival, although the prognostic ROC performance was weak-to-modest. Overall, these findings suggest that hypoxia-derived exosomal miR-4791 may contribute to TNBC progression, at least in part, through a CTCFL/PTEN-related mechanism.

DOI: https://doi.org/10.1007/s00335-026-10260-1

Oncol Res. 2026 ;34(8): 23

Breast Cancer Cell-Derived Exosomal miR-92b-3p Promotes Tumor Angiogenesis and Metastasis by Suppressing PTEN in Vascular Endothelial Cells.

Tingting Yang, Meng Guan, Xin Guan, Lihua Kang, Xiaomeng Wang, Yanjie Guan, Yang Yang, Wei Deng, Guoxiang Wang.

Background: Tumor-driven vascular remodeling is crucial for breast cancer metastasis; yet, the role of tumor-derived exosomal miRNAs in this process remains underexplored. This study aimed to investigate the clinical relevance and the underlying mechanism of breast cancer-derived exosomal miR-92b-3p in endothelial reprogramming. Methods: miR-92b-3p expression was evaluated in the TCGA cohort and clinical patient samples. The effects of exosomal miR-92b-3p from breast cancer cells on recipient human microvascular endothelial cells (HMVECs) were assessed using in vitro angiogenesis, migration, and permeability assays, alongside in vivo murine xenograft models. Mechanistic targets were validated via dual-luciferase and rescue experiments. Results: miR-92b-3p was significantly upregulated in breast cancer tissues and plasma exosomes, correlating with advanced stages, poor survival, and exhibiting high diagnostic accuracy. Breast cancer-derived exosomes effectively transferred miR-92b-3p into HMVECs, significantly promoting angiogenesis, endothelial migration, and transendothelial permeability. In vivo, overexpression of miR-92b-3p accelerated tumor growth, vascularization, and circulating tumor cell (CTC) dissemination. Mechanistically, exosomal miR-92b-3p directly targeted and suppressed PTEN in endothelial cells; moreover, restoring PTEN expression fully abrogated the exosome-induced pro-angiogenic and hyperpermeable phenotypes. Conclusions: Breast cancer-derived exosomal miR-92b-3p disrupts the vascular barrier and promotes tumor angiogenesis by targeting endothelial PTEN, thereby facilitating metastasis. Circulating exosomal miR-92b-3p represents a promising candidate liquid-biopsy biomarker for breast cancer progression.

Keywords: Breast cancer; angiogenesis; exosomes; miR-92b-3p; vascular permeability

DOI: https://doi.org/10.32604/or.2026.083563