bims-exocan 2025-01-19 papers

Issue of 2025–01–19
six papers selected by
Muhammad Rizwan, COMSATS University

Eur J Pharmacol. 2025 Jan 11. pii: S0014-2999(25)00021-4. [Epub ahead of print] 177268

Role of exosomal miRNAs and macrophage polarization in gastric cancer: a novel therapeutic strategy.

Yun Zhang, Baozhen Wang, Jing Chen, Tao Li.

Gastric cancer (GC) is one of the most common gastrointestinal cancers worldwide, with consistently high morbidity and mortality rates and poor prognosis. Most patients are diagnosed at an advanced stage due to the lack of specific presentation in the early stages. Exosomes are a class of extracellular vesicles (EVs) widely found in body fluids and can release genetic material or multiple proteins to facilitate intercellular communication. In recent years, exosomal miRNAs have gained attention for their role in various cancers. These exosomal miRNAs can impact GC development and progression by targeting specific genes or influencing signaling pathways and cytokines involved in Angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and immune regulation. They show great potential in terms of diagnosis, prognosis, and treatment of GC. Notably, the gastrointestinal tract has the largest number of macrophages, which play a significant role in GC progression. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and can influence macrophage programming through various mediators, including macrophage polarization. Macrophage polarization is involved in inflammatory responses and significantly impacts the GC process.

Keywords: Gastric cancer; exosomes; macrophages; microRNA; treatment

DOI: https://doi.org/10.1016/j.ejphar.2025.177268

Exp Cell Res. 2025 Jan 13. pii: S0014-4827(25)00020-5. [Epub ahead of print]445(1): 114424

Cancer-associated fibroblast-derived exosomes in cancer progression: A focus on hepatocellular carcinoma.

Chou-Yi Hsu, Abdulrahman T Ahmed, Safia Obaidur Rab, Subasini Uthirapathy, Suhas Ballal, Rishiv Kalia, Renu Arya, Deepak Nathiya, Muthena Kariem, Abed J Kadhim.

The tumor microenvironment (TME) has drawn much interest recently in the search for innovative cancer therapeutics, especially in light of the growing body of evidence supporting the efficacy of immune checkpoint inhibitors (ICIs). The TME comprises various cell types within the extracellular matrix (ECM), such as immune cells, endothelial cells, and cancer-associated fibroblasts (CAFs). Throughout the malignancy, these cells interact with cancerous cells and with one another. Inside the TME, CAFs are predominant and diverse cell types essential in regulating immune escape, angiogenesis, chemotherapeutic resistance, and cancer cells to invade and metastasize. Extracellular vesicles (EVs) and soluble substances are secreted by CAFs, which also remodel the extracellular matrix to partially coordinate their actions. A subclass of EVs called exosomes comprises proteins, lipids, and nucleic acids. Exosomes contain macromolecules that can transfer from one cell to another, changing the recipient cell's activity. Since exosomes are also circulating, it is possible to investigate their composition as potential biomarkers for cancer patient's diagnosis and prognosis. In this review, we focus on the function of exosomes derived from CAFs in the communications between CAFs and other TME cells and cancerous cells. Initially, we explain the various roles of CAFs in carcinogenesis. Subsequently, we address the processes by which CAFs interact with hepatocellular carcinoma (HCC) cells and other cells within the TME, with a special focus on the function of exosomes. We then go into greater detail regarding the processes by which exosomes derived from CAFs aid in the development of HCC, in addition to the clinical implications of exosomes. Finally, we address facets of exosomes that warrant additional research, such as novel discoveries regarding the enhancement of immune checkpoint inhibitor blockade therapy.

Keywords: Cancer progression; Cancer-associated fibroblasts; Exosomes; Extracellular vesicles; Hepatocellular carcinoma

DOI: https://doi.org/10.1016/j.yexcr.2025.114424

Cell Mol Biol (Noisy-le-grand). 2025 Jan 12. 70(12): 99-109

CircRNAs in extracellular vesicles associated with triple-negative breast cancer.

Ashraf Ahmed Qurtam.

Triple-negative breast cancer (TNBC) is a highly aggressive cancer with distant metastasis. Accumulated evidence has demonstrated that exosomes are involved in TNBC metastasis. Elucidating the mechanism underlying TNBC metastasis has important clinical significance. Extracellular vesicles (EVs) present a promising avenue for diagnosing and treating triple-negative breast cancer (TNBC) through a technique called "liquid biopsy," offering a new wellspring of biomarkers. These tiny lipid bilayer vesicles, released by most cells, carry a diverse array of RNA molecules that can influence the behaviour of recipient cells. Among these, circular RNAs (circRNAs) have emerged as a subtype of noncoding RNAs capable of modulating gene expression by sponging microRNAs, thus playing crucial roles in various aspects of cancer development and progression, including TNBC. Despite their significance, our understanding of circRNAs involvement in TNBC remains incomplete. However, studies have shown that circRNAs are abundant in EVs, with exosomal circRNAs (exo-circRNAs) particularly influential in cancer biology. These exo-circRNAs can be taken up by neighboring or distant cells, impacting numerous aspects of their physiological states, thereby enhancing cell communication and tumor dissemination. This review provides an overview of EVs key characteristics and functions before delving into exo-circRNAs potential roles in driving or suppressing TNBC, as well as their implications for cancer diagnosis, prognosis, and monitoring.

DOI: https://doi.org/10.14715/cmb/2024.70.12.14

Colloids Surf B Biointerfaces. 2025 Jan 06. pii: S0927-7765(25)00007-4. [Epub ahead of print]249 114500

The latest applications of exosome-mediated drug delivery in anticancer therapies.

Zhiwei Wen, Wei Zhang, Wei Wu.

In recent years, the significant role of anticancer drugs in cancer treatment has garnered considerable attention. However, the application of these drugs is largely limited by their short half-life in blood circulation, low cellular uptake efficiency, and off-target effects. Exosomes, which serve as crucial messengers in intercellular communication, exhibit unique advantages in molecular delivery compared to traditional synthetic carriers, thereby offering new possibilities for modern drug delivery systems. Exosomes possess organotropic functions and are naturally produced by cells, making them promising candidates for natural drug delivery systems with organotropic properties and minimal side effects. These naturally derived carriers can achieve stable, efficient, and selective delivery of anticancer drugs, thereby enhancing the efficacy and potential of anticancer agents in cancer immunotherapy. This review provides a concise overview of the unique characteristics of exosomes related to anticancer drug delivery, strategies for utilizing exosomes as carriers in cancer therapy, and the latest advancements in the field.

Keywords: anticancer drugs; cancer treatment; exosomes; molecular delivery

DOI: https://doi.org/10.1016/j.colsurfb.2025.114500

Mol Cancer. 2025 Jan 13. 24(1): 13

Emerging role of exosomes in cancer therapy: progress and challenges.

Jiale Li, Jiachong Wang, Zigui Chen.

This review highlights recent progress in exosome-based drug delivery for cancer therapy, covering exosome biogenesis, cargo selection mechanisms, and their application across multiple cancer types. As small extracellular vesicles, exosomes exhibit high biocompatibility and low immunogenicity, making them ideal drug delivery vehicles capable of efficiently targeting cancer cells, minimizing off-target damage and side effects. This review aims to explore the potential of exosomes in cancer therapy, with a focus on applications in chemotherapy, gene therapy, and immunomodulation. Additionally, challenges related to exosome production and standardization are analyzed, highlighting the importance of addressing these issues for their clinical application. In conclusion, exosome-based drug delivery systems offer promising potential for future cancer therapies. Further research should aim to enhance production efficiency and facilitate clinical translation, paving the way for innovative cancer treatment strategies.

Keywords: Cancer therapy; Clinical application; Exosome-based drug delivery; Exosomes

DOI: https://doi.org/10.1186/s12943-024-02215-4

Cancer Med. 2025 Jan;14(2): e70538

Improved Predictability of Diagnosis and Prognosis Using Serum- and Tissue-Derived Extracellular Vesicles From Bulk mRNA Sequencing in Pancreatic Ductal Adenocarcinoma.

Qian Zhu, Zhang Chen, Ming Tian, Xin Yan, Xiangdong Gongye, Zhicheng Liu, Anbang Zhao, Zhiyong Yang, Yufeng Yuan.

BACKGROUND: Early-stage pancreatic ductal adenocarcinoma (PDAC) is frequently misdiagnosed, contributing to its high mortality rate. Exosomal microRNAs (miRNAs) have emerged as potential biomarkers for the early detection of PDAC.
AIMS: This study aimed to evaluate the feasibility of using exosomal miRNAs from PDAC tissues and serum as biomarkers for early detection and prognosis.
MATERIALS & METHODS: Exosomes were isolated from healthy individuals and PDAC patients via tissue and serum samples, then identified by analyzing their particle size and protein content. PDAC-specific exosomal miRNAs were identified using a microRNA array. A large cohort was subsequently recruited to validate these findings. The diagnostic capacity of the identified miRNAs was assessed using the Brier score and area under the curve (AUC). Verified miRNAs were also used to confirm intracellular mRNA change patterns.
RESULTS: The combination of miR142-3p, miR148a-3p, and CA199 showed a higher AUC (0.747) compared to CA199 alone (0.716) in ROC curve analysis. Gene Ontology (GO) annotations revealed that the two-miRNA panel was associated with multiple oncogenic pathways.
DISCUSSION: 142-3p and miR148a-3p were identified as specific to PDAC and, when combined with CA199, improved diagnostic accuracy. Their involvement in oncogenic pathways underscores their relevance as diagnostic and prognostic biomarkers.
CONCLUSION: MiR142-3p and miR148a-3p, alongside CA199, show promise as non-invasive biomarkers for early detection and prognosis of PDAC, improving diagnostic accuracy.

Keywords: Exosomal miRNA; PDAC; diagnosis; exosome; prognosis

DOI: https://doi.org/10.1002/cam4.70538