Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Dec. 22, 2022

Cancer divergence has many facets other than being considered a genetic term. It is tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates opportunity explore possible mechanism surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, fibroblast cells. stem cells (CSCs) or stem-like small sub-set population within believed be responsible player self-renewal, metastasis, The correlation between CSCs remains an enigma understanding events resistance biology. Recent evidence suggests that dictates maintenance arbitrate progression metastasis. adipocyte, release growth factors, cytokines, chemokines, microRNAs, exosomes provide cues for gain CSC features. These intricate cross-talks fueled evolve into aggressive, invasive, migratory phenotypes development. In this review, we have abridged recent developments role factors how these influence transition further translate cancer.

Language: Английский

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Exosomal circular RNAs: A chief culprit in cancer chemotherapy resistance

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 67, P. 100937 - 100937

Published: Feb. 2, 2023

Language: Английский

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Exosomal circRNA: emerging insights into cancer progression and clinical application potential

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

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Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(5), P. 1263 - 1321

Published: March 23, 2023

Abstract Gastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number deaths worldwide. STAT3 is an oncogenic transcription factor that promotes genes associated with proliferation, antiapoptosis, survival, metastasis. overactivated in many human malignancies including GI which accelerates tumor progression, metastasis, drug resistance. Research recent years demonstrated noncoding RNAs (ncRNAs) play major role regulation signaling pathways pathway. The types endogenous ncRNAs are being extensively studied oncology microRNAs, long RNAs, circular RNAs. These can either be tumor‐promoters or tumor‐suppressors each one them imparts their activity via different mechanisms. pathway also tightly modulated by ncRNAs. In this article, we have elaborated on tumor‐promoting tumors. Subsequently, comprehensively discussed as well suppressor functions mechanism action known modulate cancers.

Language: Английский

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Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 4, 2024

Abstract Current treatment strategies for cancer, especially advanced are limited and unsatisfactory. One of the most substantial advances in cancer therapy, last decades, was discovery a new layer immunotherapy approach, immune checkpoint inhibitors (ICIs), which can specifically activate cells by targeting checkpoints. Immune checkpoints type immunosuppressive molecules expressed on cells, regulate degree activation avoid autoimmune responses. ICIs, such as anti-PD-1/PD-L1 drugs, has shown inspiring efficacy broad applicability across various cancers. Unfortunately, not all patients benefit remarkably from overall response rates to ICIs remain relatively low types. Moreover, primary acquired resistance pose serious challenges clinical application immunotherapy. Thus, deeper understanding molecular biological properties regulatory mechanisms is urgently needed improve options fo r current therapies. Recently, circular RNAs (circRNAs) have attracted increasing attention, only due their involvement aspects hallmarks, but also impact shaping tumor microenvironment. In this review, we systematically summarize status existing roles circRNAs Meanwhile, aim settle issue an evidence-oriented manner that involved hallmarks effects

Language: Английский

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Regulation of cancer-associated fibroblasts for enhanced cancer immunotherapy using advanced functional nanomedicines: an updated review

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 4, 2025

The tumor microenvironment (TME) is a complex and dynamic ecosystem that plays critical role in cancer progression. It comprises various cell types, including immune cells, stromal cells. Among these, cancer-associated fibroblasts (CAFs) represent heterogeneous population with diverse origins, phenotypes, functions. Activated CAFs secrete multiple factors promote growth, migration, angiogenesis, contribute to chemoresistance. Additionally, extracellular matrix (ECM) components, such as collagen, which form physical barrier hinders the penetration of chemotherapeutic immunotherapeutic agents. This ECM also influences infiltration, impeding their ability effectively target As result, modulating activity has emerged promising strategy enhance efficacy immunotherapy. Nano-delivery systems, constructed from nanomaterials high targeting specificity biocompatibility, offer compelling approach deliver therapeutic agents or immunomodulatory directly CAFs. modulation can alter CAF function, reduce tumor-promoting effects, thereby improve outcomes review provides an in-depth exploration functions, interactions within TME, particularly context suppression. Furthermore, it discusses potential applications functional nanocarrifers enhancing effectiveness immunotherapy, highlighting significant progress nanotechnology this area.

Language: Английский

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Exosomal circRNAs in cancer: Implications for therapy resistance and biomarkers

Cancer Letters, Journal Year: 2023, Volume and Issue: 566, P. 216245 - 216245

Published: May 27, 2023

Language: Английский

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Recent advances of exosomal circRNAs in cancer and their potential clinical applications

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 31, 2023

Abstract Circular RNA (circRNA) is a type of non-coding that forms covalently closed, uninterrupted loop. The expression circRNA differs among cell types and tissues, various circRNAs are aberrantly expressed in variety diseases, including cancer. Aberrantly contribute to disease progression by acting as microRNA sponges, functional protein or novel templates for translation. Recent studies have shown enriched exosomes. Exosomes spherical bilayer vesicles released cells into extracellular spaces mediate intercellular communication delivering cargoes. These cargoes include metabolites, proteins, lipids, molecules. Exosome-mediated cell-cell cell-microenvironment communications influence the carcinogenesis regulating proliferation, angiogenesis, metastasis well immune escape. In this review, we summarize current knowledge about exosomal cancers discuss their specific functions tumorigenesis. Additionally, potential value diagnostic biomarkers applications circRNA-based cancer therapy.

Language: Английский

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Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: April 21, 2023

Abstract Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and most common form liver cancer. Treatment HCC depends on chemotherapy, radiotherapy, surgery, immunotherapy, all which have their own drawbacks, patients may develop resistance these therapies due aggressive behavior cells. New effective for can be developed by targeting molecular signaling pathways. The expression signal transducer activator transcription 3 (STAT3) in cancer cells changes, during progression, tends increase. After induction STAT3 growth factors cytokines, phosphorylated translocated nucleus regulate progression. concept current review revolves around phosphorylation status HCC, studies show that high progression HCC. This addresses function as an oncogenic factor able prevent apoptosis thus promote Moreover, regulates both survival- death-inducing autophagy promotes metastasis inducing epithelial–mesenchymal transition (EMT). In addition, upregulation associated with occurrence chemoresistance radioresistance Specifically, non-protein-coding transcripts inhibition antitumor agents affect tumor this review, topics are discussed detail provide further insight into role tumorigenesis, treatment resistance, pharmacological regulation Graphical

Language: Английский

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Extracellular vesicle-packaged circBIRC6 from cancer-associated fibroblasts induce platinum resistance via SUMOylation modulation in pancreatic cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Nov. 28, 2023

Abstract Background Cancer-associated fibroblasts (CAFs) play pivotal roles in chemoresistance of pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanisms are poorly understood. Revealing cross-talk network between tumor stroma and cancer developing effective strategies against oxaliplatin resistance highly desired clinic. Methods High-throughput sequence was used to screened key circRNAs transmitted by extracellular vesicles (EVs) from CAFs cells. The associations EV-packaged circBIRC6 chemotherapy responsiveness were validated a cohort 82 cases advanced PDAC patients. Then, effects on CAF-induced investigated flow cytometry, colony formation, viability organoids vitro xenograft models vivo. RNA pulldown, immunoprecipitation, sites mutation assays reveal mechanism. Results We identified circRNA, circBIRC6, is significantly upregulated CAF-derived EVs positively associated with oxaliplatin-based chemoresistance. In vivo functional showed that enhance cells via regulating non-homologous end joining (NHEJ) dependent DNA repair. Mechanistically, directly binds XRCC4 enhanced interaction SUMO1 at lysine 115 residue, which facilitated chromatin localization. K115R dramatically abrogated induced effect. Moreover, combination antisense oligonucleotide inhibitors Olaparib suppressed patient-derived models. Conclusions Our study revealed confer mediating SUMOylation XRCC4, introducing promising predictive therapeutic target for resistance.

Language: Английский

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