Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications DOI Creative Commons
Zhengjun Lin, Guoqing Li, Ke Jiang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 7, 2024

Cancer-associated fibroblasts (CAFs) are a diverse stromal cell population within the tumour microenvironment, where they play fundamental roles in cancer progression and patient prognosis. Multiple lines of evidence have identified that CAFs critically involved shaping structure function microenvironment with numerous functions regulating behaviours, such as metastasis, invasion, epithelial-mesenchymal transition (EMT). can interact extensively cells by producing extracellular vesicles (EVs), multiple secreted factors, metabolites. Notably, CAF-derived EVs been critical mediators therapy resistance, constitute novel targets biomarkers management. This review aimed to summarize biological detailed molecular mechanisms mediating resistance chemotherapy, targeted agents, radiotherapy, immunotherapy. We also discussed therapeutic potential clinical management, thereby providing strategy for enhancing efficacy improving

Language: Английский

Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs DOI Creative Commons
Ran Qi,

Yixuan Bai,

Kun Li

et al.

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 68, P. 100960 - 100960

Published: March 28, 2023

Pancreatic cancer continues to be one of the world's most lethal cancers. Chemotherapy resistance in patients with advanced pancreatic often accompany dismal prognosis, highlighting need investigate mechanisms drug and develop therapies overcome chemoresistance.This research was filed Chinese Clinical Trial Registry (ChiCTR2200061320). In order isolate primary normal fibroblasts (NFs) cancer-associated (CAFs) samples ductal adenocarcinoma (PDAC) paracancerous tissue from individuals diagnosed PDAC were obtained. The exosomes obtained using ultracentrifugation, their characteristics determined by Western blotting, nanoparticle tracking analysis, transmission electron microscopy. CAF-derived miRNAs analyzed RT-qPCR high-throughput sequencing. Gemcitabine (GEM) employed promote ferroptosis, ferroptosis levels monitoring lipid reactive oxygen species (ROS), cell survival, intracellular Fe2+ concentrations. To assess vivo tumor response GEM therapy, a xenograft mouse model utilized.Exosomes derived CAFs did not exhibit innate resistance. promoted chemoresistance cells following treatment secreting exosomes, maintaining signaling communication cells. Mechanistically, miR-3173-5p CAF sponged ACSL4 inhibited after uptake cells.This work demonstrates novel mode acquired identifies miR-3173-5p/ACSL4 pathway as promising target for GEM-resistant cancer.

Language: Английский

Citations

143
Extracellular Vesicles: New Classification and Tumor Immunosuppression DOI Creative Commons
Mona Sheta, Eman A. Taha,

Yanyin Lu

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(1), P. 110 - 110

Published: Jan. 10, 2023

Extracellular vesicles (EVs) are cell-derived membrane-surrounded carrying various types of molecules. These EV cargoes often used as pathophysiological biomarkers and delivered to recipient cells whose fates altered in local distant tissues. Classical EVs exosomes, microvesicles, apoptotic bodies, while recent studies discovered autophagic EVs, stressed matrix vesicles. Here, we classify classical new non-EV nanoparticles. We also review EVs-mediated intercellular communication between cancer tumor-associated cells, such cancer-associated fibroblasts, adipocytes, blood vessels, lymphatic immune cells. Of note, play crucial roles immunosuppression, evasion, immunotherapy resistance. Thus, change hot tumors into cold ones. Moreover, affect nonimmune promote cellular transformation, including epithelial-to-mesenchymal transition (EMT), chemoresistance, tumor production, destruction biological barriers, angiogenesis, lymphangiogenesis, metastatic niche formation.

Language: Английский

Citations

113
Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer DOI Creative Commons
Lin Shi, Weiliang Zhu,

Yuanyuan Huang

et al.

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(7)

Published: July 1, 2022

Cancer-associated fibroblasts (CAFs) contributes to overall tumor progression. In the current survey, we explored ability of microRNA-20a (miR-20a) within these CAF-derived exosomes influence non-small-cell lung cancer (NSCLC)

Language: Английский

Citations

104
Exosomal circRNA: emerging insights into cancer progression and clinical application potential DOI Creative Commons
Fan Zhang, Jiajia Jiang, Hui Qian

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 26, 2023

Abstract Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune fibroblasts, other components, thereby regulating critical aspects of cancer progression including escape, angiogenesis, metabolism, drug resistance, proliferation metastasis. Interestingly, microenvironment have new findings in influencing escape mediated by the release exosomal circRNA. Given intrinsic stability, abundance, broad distribution circRNAs, they represent excellent diagnostic prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up possibilities therapy, potentially bolstered nanoparticles or plant exosome delivery strategies. In this review, we summarize functions underlying mechanisms cell non-tumor cell-derived progression, with special focus on their roles immunity metabolism. Finally, examine potential application therapeutic targets, highlighting promise clinical use.

Language: Английский

Citations

96
Notch signaling pathway in cancer: from mechanistic insights to targeted therapies DOI Creative Commons

Qingmiao Shi,

Chen Xue,

Yifan Zeng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Language: Английский

Citations

84
Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications DOI Creative Commons

Yang Qiu-rong,

Jing Xu, Jianmei Gu

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(34)

Published: Oct. 17, 2022

Abstract Extracellular vesicles (EVs) are cell‐derived nanosized that mediate cell‐to‐cell communication via transporting bioactive molecules and thus critically involved in various physiological pathological conditions. EVs contribute to different aspects of cancer progression, such as growth, angiogenesis, metastasis, immune evasion, drug resistance. induce the resistance cells chemotherapy, radiotherapy, targeted therapy, antiangiogenesis immunotherapy by transferring specific cargos affect efflux regulate signaling pathways associated with epithelial‐mesenchymal transition, autophagy, metabolism, stemness. In addition, modulate reciprocal interaction between noncancer tumor microenvironment (TME) develop therapy detectable many biofluids patients, regarded novel biomarkers for monitoring response predicting prognosis. Moreover, suggested promising targets engineered nanovehicles deliver drugs overcoming therapy. this review, biological roles their mechanisms action summarized. The preclinical studies on using also discussed.

Language: Английский

Citations

82
Dysregulated Signalling Pathways Driving Anticancer Drug Resistance DOI Open Access

Nauf Bou Antoun,

Athina‐Myrto Chioni

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12222 - 12222

Published: July 30, 2023

One of the leading causes death worldwide, in both men and women, is cancer. Despite significant development therapeutic strategies, inevitable emergence drug resistance limits success impedes curative outcome. Intrinsic acquired are common mechanisms responsible for cancer relapse. Several factors crucially regulate tumourigenesis resistance, including physical barriers, tumour microenvironment (TME), heterogeneity, genetic epigenetic alterations, immune system, burden, growth kinetics undruggable targets. Moreover, transforming factor-beta (TGF-β), Notch, epidermal factor receptor (EGFR), integrin-extracellular matrix (ECM), nuclear kappa-light-chain-enhancer activated B cells (NF-κB), phosphoinositol-3-kinase/protein kinase B/mammalian target rapamycin (PI3K/Akt/mTOR), wingless-related integration site (Wnt/β-catenin), Janus kinase/signal transducers activators transcription (JAK/STAT) RAS/RAF/mitogen-activated protein (MAPK) signalling pathways some key players that have a pivotal role mechanisms. To guide future treatments improve results, deeper comprehension necessary. This review covers intrinsic gives comprehensive overview recent research on enable to bypass barriers put up by treatments, and, like “satellite navigation”, find alternative routes which carry their “journey” progression.

Language: Английский

Citations

46
Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation DOI Creative Commons
Fei Ren, Qian Fei,

Kun Qiu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: April 1, 2024

Abstract Lung cancer stands as the most prevalent form of globally, posing a significant threat to human well-being. Due lack effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still potential means eradicating cancer, usually miss best chance for treatment, even after may experience tumor recurrence. Additionally, chemotherapy, mainstay treatment has be chemo-resistant, resulting in poor clinical outcomes. The emergence liquid biopsies garnered considerable attention owing their noninvasive nature ability continuous sampling. Technological advancements have propelled circulating cells (CTCs), DNA (ctDNA), extracellular vesicles (EVs), metabolites, tumor-educated platelets (TEPs), tumor-associated antigens (TAA) forefront key biopsy biomarkers, demonstrating intriguing encouraging results diagnosis prognostic evaluation This review provides an overview molecular biomarkers assays utilized encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, TAAs TEPs. Furthermore, we expound on practical applications biopsies, including diagnosis, response monitoring, evaluation, recurrence monitoring context

Language: Английский

Citations

37
Dynamic interactions in the tumor niche: how the cross-talk between CAFs and the tumor microenvironment impacts resistance to therapy DOI Creative Commons
Oliwia Piwocka, Igor Piotrowski, Wiktoria Maria Suchorska

et al.

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 22, 2024

The tumor microenvironment (TME) is a complex ecosystem of cells, signaling molecules, and extracellular matrix components that profoundly influence cancer progression. Among the key players in TME, cancer-associated fibroblasts (CAFs) have gained increasing attention for their diverse influential roles. CAFs are activated found abundantly within TME various types. contribute significantly to progression by promoting angiogenesis, remodeling matrix, modulating immune cell infiltration. In order microenvironment, engage cross-talk with other stromal through paracrine direct cell-cell interactions. This can result immunosuppression, proliferation, epithelial-mesenchymal transition, contributing disease Emerging evidence suggests play crucial role therapy resistance, including resistance chemotherapy radiotherapy. modulate response treatment secreting factors promote drug efflux, enhance DNA repair mechanisms, suppress apoptosis pathways. paper aims understand multifaceted functions discusses between sheds light on contibution resistance. Targeting or disrupting cells holds promise overcoming improving efficacy

Language: Английский

Citations

19
Cancer-associated fibroblast-derived extracellular vesicles: regulators and therapeutic targets in the tumor microenvironment DOI Open Access
Jindong Xie, Xinmei Lin, Xinpei Deng

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Cancer-associated fibroblasts (CAFs) constitute a critical component of the tumor microenvironment (TME). CAFs can be reprogrammed by cancer cells, leading to production extracellular vesicles (EVs). These EVs serve as carriers for bioactive substances, including proteins, nucleic acids, and metabolic products, thereby facilitating progression. CAF-derived exert substantial influence on cell proliferation, invasion, metastasis, immunological environment, processes lymphangiogenesis angiogenesis. Despite their potential non-invasive biomarkers therapeutic delivery vehicles, clinical application is currently limited challenges in purification precise targeting. This review delineates diverse roles growth, immune evasion within TME.

Language: Английский

Citations

2