bims-exocan 2026-06-07 papers

Issue of 2026–06–07
six papers selected by
Muhammad Rizwan, COMSATS University

Small. 2026 May 30. e73721

Exosomes in Glioma: Integrating Molecular Mechanisms with Diagnostic and Therapeutic Potential.

Yantong Liu, Yingdi Nie, Hao Zhang, Wantao Wu, Nan Zhang, Zhiwei Xia, Jianping Wen, Peng Luo, Quan Cheng.

Glioma, a lethal intracranial malignancy with limited therapeutic options, represents one of oncology's most persistent challenges. Entering a new era of molecular oncology, exosomes-nanoscale extracellular vesicles-have emerged as master regulators of intercellular communication, dynamically sculpting the glioma tumor microenvironment (TME) and orchestrating hallmarks of malignancy, including immune evasion, angiogenesis, and therapeutic resistance. These versatile vesicles transport bioactive cargo (e.g., miRNAs, lncRNAs, proteins) to reprogram stromal, neuronal, and immune cells, creating a permissive niche for tumor progression. Recent breakthroughs now position exosomes at the forefront of translational medicine, serving dual roles as minimally invasive biomarkers and engineered nanovectors for precision therapy. This review systematically deciphers how exosomes fuel glioma pathogenesis-from driving macrophage polarization and T-cell suppression to facilitating blood-brain barrier disruption and chemoresistance. Beyond mechanistic insights, we spotlight pioneering strategies harnessing exosomes for drug delivery, immunotherapy, and nanotechnology-driven interventions. By bridging foundational discoveries with clinical applications, this work heralds a new era in glioma management, where exosome-based tools promise to revolutionize personalized diagnosis, prognostication, and therapeutic innovation.

Keywords: exosome; glioma; precision medicine; tumor microenvironment

DOI: https://doi.org/10.1002/smll.73721

J Nanobiotechnology. 2026 May 30.

Extracellular vesicle and particle biomarkers in cancer: a machine learning blueprint for liquid biopsy.

Jinling Yu, Gen Xu, Yu Li, Mingyao Huang, Liang Yang, Xueqiang Peng.

The combination of machine learning and liquid biopsy is rapidly promoting the development of precision cancer diagnosis. Extracellular vesicles and particles (EVPs) are liquid biopsy markers with great diagnostic value due to their unique structure, high stability and strong disease specificity in body fluids. With the rapid development of artificial intelligence (AI), machine learning enables the identification of informative biomarkers from high-dimensional, complex, and large-scale biological data. Thanks to this, EVPs have made rapid progress in the correlation research of tumor diagnosis and prognosis evaluation in recent years. This review focuses on cancer, the area in which liquid biopsy is most extensively studied and clinically needed. This review focuses on cancer as a primary application domain of liquid biopsy and provides a structured overview of machine learning methodologies in this context. We summarize recent advances in feature mining, multi-omics integration, and multi-marker fusion strategies for blood- and EVP-derived data, while also discussing key challenges, including data heterogeneity, model interpretability, and clinical validation.

Keywords: Cancer diagnosis; Extracellular vesicles (EVs); Liquid biopsy; Machine learning; Precision oncology

DOI: https://doi.org/10.1186/s12951-026-04525-9

Mol Biol Rep. 2026 Jun 02. pii: 872. [Epub ahead of print]53(1):

Nanomedicine in precision treatment of gastric cancer: current clinical landscape.

ShengJin Tu, Xiao Dong Wang, Hua Yang.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with therapeutic efficacy often hindered by late-stage diagnosis, chemoresistance, and the immunosuppressive tumor immune microenvironment (TIME). This review systematically evaluates the current clinical landscape and emerging breakthroughs in nanomedicine-based interventions for GC. We discuss how unique pathological features of the GC microenvironment such as hypoxia, acidity, and dense stroma-are leveraged to design "smart" stimuli-responsive nanoplatforms for precise drug delivery. Furthermore, the review highlights innovative strategies for TIME remodeling, including macrophage repolarization, cGAS-STING pathway activation, and the integration of multimodal therapies like chemo-photodynamic and immunotherapy. Beyond therapeutics, we examine the pivotal role of nanotechnology in advancing early diagnosis through ultrasensitive biosensors and multimodal imaging probes. Clinically, the successful application of nanoparticle albumin-bound (nab)-paclitaxel underscores the potential of nanomedicine to enhance safety and efficacy. By integrating artificial intelligence (AI) and machine learning for patient stratification, nanomedicine is poised to reshape precision oncology in GC. This review concludes that while challenges in clinical translation persist, the development of bio-inspired nanoplatforms offers a promising frontier for improving the prognostic outlook of gastric cancer patients.

Keywords: Clinical translation; Gastric cancer; Nanomedicine; Precision treatment; Targeted drug delivery; Tumor immune microenvironment

DOI: https://doi.org/10.1007/s11033-026-12068-3

Cancer Med. 2026 Jun;15(6): e72000

Exosomal miR-4644 Targets SPRY3 to Promote Proliferation and Invasion of Pancreatic Cancer.

Xiangyu Chu, Dongqi Li, Fusheng Zhang, Yongsu Ma, Yongqi Deng, Chen Wang, Xiaodong Tian, Yanlian Yang, Yinmo Yang.

BACKGROUND: Tumor-derived exosomes (TDEs) can carry diverse genetic material that modulates pancreatic cancer (PC) proliferation and invasion. Despite this, the involvement of microRNAs (miRNAs) in TDE-mediated tumor progression in PC remains inadequately explored.
METHODS: Ultracentrifugation was used to isolate exosomes derived from AsPC-1 and BxPC-3 cells. Cell proliferation was assessed by cell counting kit-8 (CCK-8) and plate colony formation assays. Cell migration and invasion were evaluated using Transwell assays. Real-time polymerase chain reaction (RT-PCR) was performed to detect the expression levels of miR-4644 and Sprouty RTK Signaling Antagonist 3 (SPRY3). A dual-luciferase reporter assay was conducted to verify the binding site between miR-4644 and SPRY3. Orthotopic PC xenografts were established to validate the effects of SPRY3 and miR-4644. Finally, the relative expression levels of SPRY3 were validated using PC tissue and matched adjacent non-tumor tissue samples.
RESULTS: MiR-4644 was enriched in TDEs, and the inhibition of miR-4644 reduced the proliferation, migration, and invasion of PC cells. SPRY3 was identified as a direct target of miR-4644, which bound to the 3'-UTR of SPRY3 and suppressed its expression. The inhibitory effects of SPRY3 on PC cell proliferation, migration, and invasion were partially counteracted by miR-4644. Importantly, clinical data analysis revealed that SPRY3 expression was significantly downregulated in PC tissues (p < 0.05). Mechanistically, miR-4644 targeted SPRY3 and promoted PC cell proliferation, migration, and invasion through the Ras-Raf-MAPK signaling pathway.
CONCLUSIONS: MiR-4644 is upregulated in PC TDEs and promotes PC cell progression by suppressing SPRY3 expression; high expression of exosomal miR-4644 correlates with poor patient prognosis.

DOI: https://doi.org/10.1002/cam4.72000

Cancer Lett. 2026 May 30. pii: S0304-3835(26)00388-5. [Epub ahead of print]655 218625

Exosomal circFXR1 drives immune evasion and tumor progression through dual regulation of PD-L1 and mTOR signaling in gastric cancer.

Hongwu Chu, Xin Liu, Xiaomei Zhuang, Fulin Wang, Ian M Evans, Yuntao Shi, Chen Wang, Junkui Guo, Huafu Li, Zhijun Zhou, Cuncan Deng, Changhua Zhang.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, largely due to aggressive tumor behavior, immune evasion, and limited responsiveness to immunotherapy. Circular RNAs (circRNAs) have emerged as important regulators of cancer progression; however, the roles of exosomal circRNAs in tumor-immune communication in GC remain poorly understood. Here, circRNA profiling of exosomes derived from GC tissues and matched adjacent normal tissues identified circFXR1 as an upregulated circRNA associated with poor survival and adverse clinicopathological features. Functional analyses using GC cell lines, patient-derived organoid, and multiple mouse models demonstrated that circFXR1 promotes tumor proliferation, migration, and growth both in vitro and in vivo. Mechanistically, circFXR1 interacts with miR-497-5p, thereby upregulating PD-L1 expression, which in turn impairs CD8+ T cell-mediated cytotoxicity. In parallel, circFXR1 activates tumor-intrinsic mTOR signaling in a miR-497-5p-dependent manner, further enhancing malignant phenotypes. Importantly, circFXR1 is enriched in tumor-derived exosomes and transferred to recipient tumor cells and CD8+ T cells, resulting in increased PD-L1 expression, impaired T cell effector function, and enhanced tumor progression. Clinically, circFXR1 expression was elevated in non-responders compared with responders to anti-PD-1 therapy. Consistently, in an NSG xenograft model with adoptive transfer of human CD8+ T cells, circFXR1 overexpression attenuated the therapeutic efficacy of anti-PD-1 treatment. Collectively, these findings identify exosomal circFXR1 as a regulator linking tumor-intrinsic signaling and CD8+ T cell-associated immune evasion in GC. CircFXR1 may be associated with anti-PD-1 treatment response in GC, although further validation in molecularly stratified, multi-center cohorts is required.

Keywords: Exosomes; Gastric cancer; PD-L1; circFXR1; mTOR signaling

DOI: https://doi.org/10.1016/j.canlet.2026.218625

Drug Resist Updat. 2026 Jun 01. pii: S1368-7646(26)00072-5. [Epub ahead of print]87 101421

PRKCA and ABCB1 dual-enriched exosomes are key drivers of drug resistance in chronic myeloid leukemia.

Fei Li, Jin-Fei Lin, Peng Tian, Haisheng Chen, Qian Yang, Qiqi Guo, Jiasheng Wang, Yue He, Junru Chen, Xiaojian Hu, Chunmou Li, Weitong Mai, Menghan Duan, Michael Peng, Zackary Rousseau, Chun Chen, Heyu Ni, Qing Zhang.

AIMS: Drug resistance frequently results in treatment failure for leukemia and leads to the progression of chronic myeloid leukemia (CML) into an accelerated or blast phase. An increasing number of CML cases exhibit reduced responsiveness or are refractory to tyrosine kinase inhibitors and chemotherapeutic drugs. Exosomes, as intercellular communication carriers, have been shown to participate in various forms of tumor drug resistance, but their role and mechanisms in CML drug resistance have not yet been fully investigated.
METHODS: Exosomes were isolated from the cell culture medium or plasma using ultracentrifugation. RNA sequencing, LC-MS proteomics, Western blot, molecular docking, co-immunoprecipitation, cell viability assay, and flow cytometry analysis were carried out to examine the mechanisms of exosomes in CML drug resistance. Cell line-derived and patient-derived xenografts were estimated to verify the mechanisms of exosomes in CML drug resistance in vivo. Clinical samples from CML patients were used to analyze the predictive potential of exosomes in CML drug resistance.
RESULTS: Drug-resistant CML cell-derived exosomes promote multifaceted resistance to imatinib and doxorubicin by directly disseminating the ATP-binding cassette subfamily B member 1 (ABCB1) efflux pump to initially sensitive cells and indirectly upregulating ABCB1 expression, enhancing drug expulsion and resistance. The specific binding regions between ABCB1 with protein kinase C-alpha (PRKCA) that is required for dual-enriched exosomal packaging and ABCB1-mediated resistance. We identified myristoylated alanine-rich C kinase substrate (MARCKS) regulation of PRKCA is an essential prerequisite to PRKCA-ABCB1 interaction, forming a tri-protein complex in drug-resistant CML cells that selectively enriches PRKCA and ABCB1 into exosomes. Mechanistically, exosomes enriched with both PRKCA and ABCB1 enhance fatty acid metabolism through PRKCA, activate the AGE-RAGE signaling pathway, and subsequently upregulate the transcription factors ETS1 and FOXA1. This process leads to increased expression of PRKCA and ABCB1 in drug-sensitive cells, which further contribute to drug efflux and drug resistance in CML cells. Clinically, plasma exosomal PRKCA and ABCB1 together accurately predict drug resistance in CML patients.
CONCLUSIONS: PRKCA and ABCB1 dual-enriched exosomes are key drivers of drug resistance in CML patients, and exosomal PRKCA and ABCB1 may serve as diagnostic and therapeutic targets for CML.

Keywords: ABCB1; Chronic myeloid leukemia; Drug resistance; Exosomes; PRKCA

DOI: https://doi.org/10.1016/j.drup.2026.101421