Chemoresistance and the tumor microenvironment: the critical role of cell–cell communication

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 10, 2024

Resistance of cancer cells to anticancer drugs remains a major challenge in modern medicine. Understanding the mechanisms behind development chemoresistance is key developing appropriate therapies counteract it. Nowadays, with advances technology, we are paying more and attention role tumor microenvironment (TME) intercellular interactions this process. We also know that important elements TME not only themselves but other cell types, such as mesenchymal stem cells, cancer-associated fibroblasts, stromal macrophages. can communicate each indirectly (via cytokines, chemokines, growth factors, extracellular vesicles [EVs]) directly gap junctions, ligand-receptor pairs, adhesion, tunnel nanotubes). This communication appears be critical for chemoresistance. EVs seem particularly interesting structures regard. Within these structures, lipids, proteins, nucleic acids transported, acting signaling molecules interact numerous biochemical pathways, thereby contributing Moreover, drug efflux pumps, which responsible removing from transported via EVs.

Language: Английский

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Hypoxia-Inducible Factor-Dependent and Independent Mechanisms Underlying Chemoresistance of Hypoxic Cancer Cells

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1729 - 1729

Published: April 29, 2024

In hypoxic regions of malignant solid tumors, cancer cells acquire resistance to conventional therapies, such as chemotherapy and radiotherapy, causing poor prognosis in patients with cancer. It is widely recognized that some the key genes behind this are hypoxia-inducible transcription factors, e.g., factor 1 (HIF-1). Since HIF-1 activity suppressed by two representative 2-oxoglutarate-dependent dioxygenases (2-OGDDs), PHDs (prolyl-4-hydroxylases), FIH-1 (factor inhibiting 1), inactivation 2-OGDD has been associated therapy activation HIF-1. Recent studies have also revealed importance hypoxia-responsive mechanisms independent its isoforms (collectively, HIFs). article, we collate accumulated knowledge HIF-1-dependent responsible for anticancer drugs briefly discuss interplay between hypoxia responses, like EMT UPR, chemoresistance. addition, introduce a novel HIF-independent mechanism, which epigenetically mediated an acetylated histone reader protein, ATAD2, recently clarified.

Language: Английский

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Novel insights into taxane pharmacology: an update on drug resistance mechanisms, immunomodulation and drug delivery strategies

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 81, P. 101223 - 101223

Published: March 8, 2025

Taxanes are effective in several solid tumors. Paclitaxel, the main clinically available taxane, was approved early nineties, for treatment of ovarian cancer and later on, together with analogs docetaxel cabazitaxel, other malignancies. By interfering microtubule function impairing separation sister cells at mitosis, taxanes act as antimitotic agents, thereby counteracting high proliferation rate cells. The action goes beyond their because cellular targets, microtubules, participate multiple processes such intracellular transport cell shape maintenance. clinical efficacy is limited by development resistance mechanisms. Among these, extracellular vesicles have emerged new players. In addition, taxane metronomic schedules shows an impact on tumor microenvironment reflected antiangiogenic immunomodulatory effects, aspect growing interest considering inclusion regimens immunotherapeutics. Preclinical studies paved bases synergistic combinations both conventional targeted agents. A variety drug delivery strategies provided novel opportunities to increase activity. ability orchestrate different effects amenable modulation suggests options improve cures lethal

Language: Английский

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CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY: HARNESSING EXTRACELLULAR VESICLES FOR ENHANCED EFFICACY

Pharmacological Research, Journal Year: 2024, Volume and Issue: 208, P. 107352 - 107352

Published: Aug. 13, 2024

A cutting-edge approach in cell-based immunotherapy for combating resistant cancer involves genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes. In recent years, these therapies have demonstrated effectiveness, leading to their commercialization and clinical application against certain types of cancer. However, CAR-T therapy faces limitations, such as the immunosuppressive tumour microenvironment (TME) that can render cells ineffective, adverse side effects therapy, including cytokine release syndrome (CRS). Extracellular vesicles (EVs) are a diverse group membrane-bound particles released into extracellular environment by virtually all cell types. They essential intercellular communication, transferring cargoes proteins, lipids, various RNAs, DNA fragments target cells, traversing biological barriers both locally systemically. EVs play roles numerous physiological processes, with those from immune non-immune capable modulating system through activation or suppression. Leveraging this capability enhance could represent significant advancement overcoming its current limitations. This review examines landscape explores potential role augmenting therapeutic efficacy.

Language: Английский

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New insights of LncRNAs fingerprints in breast cancer progression: Tumorigenesis, drug resistance, and therapeutic opportunities

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 287, P. 138589 - 138589

Published: Dec. 9, 2024

Breast cancer (BC) is one of the common female cancers and it characterized by considerable problems regarding its development therapy. Long non-coding RNAs (lncRNAs) have been identified as significant modulators in BC development, especially, tumorigenicity chemoresistance. We therefore endeavor to present an up-to-date understanding lncRNAs their impact on progression treatment, concerning molecular processes, treatment options, use a therapeutic opportunity. LncRNAs are novel regulators genes that cause resistance directly functioning both coding patients, but little known about mechanisms actions. Thus, additional study required deeper modes action possible roles disease. This aims investigate functions BC, with particular attention role tumorigenesis, drug mechanisms, targets. will help identify targets improve effectiveness treatment.

Language: Английский

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Hypoxia as a critical player in extracellular vesicles-mediated intercellular communication between tumor cells and their surrounding microenvironment

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1880(1), P. 189244 - 189244

Published: Dec. 11, 2024

In the past years, increasing attention has been paid to role of extracellular vesicles (EVs) as mediators intercellular communication in cancer. These small size particles mediate transfer important bioactive molecules involved malignant initiation and progression. Hypoxia, or low partial pressure oxygen, is recognized a remarkable feature solid tumors demonstrated exert profound impact on tumor prognosis therapeutic efficacy. Indeed, high-pitched growth rate chaotic neovascular architecture that embodies results reduction oxygen within microenvironment (TME). response oxygen-deprived conditions, cells their surrounding milieu develop homeostatic adaptation mechanisms contribute establishment pro-tumoral phenotype. Latest evidence suggests hypoxic surrounds bulk may be clincher for observed elevated levels circulating EVs cancer patients. Thus, it proposed play mediating conditions. This review focuses EVs-mediated crosstalk established between immune, endothelial, stromal cell populations, TME.

Language: Английский

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The role of miRNAs in the extracellular vesicle-mediated interplay between breast tumor cells and cancer-associated fibroblasts

Journal of Cancer Metastasis and Treatment, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

The tumor microenvironment (TME) of breast cancer (BC) is depicted as an immunosuppressive dwelling that comprises a myriad cell types embedded in the extracellular matrix. As one most abundant populations within TME, cancer-associated fibroblasts (CAFs) play indispensable roles increasing aggressiveness and promoting resistance to standard-of-care therapies. Extracellular vesicles (EVs) represent diverse array biological nanoparticles, encompassing exosomes, microvesicles, apoptotic bodies. In recent years, these cell-derived membranous structures have raised great interest they can encapsulate numerous cellular cargo, such proteins, lipids, miRNAs. By transmitting bioactive content recipient cells, EVs pivotal intercellular communication between CAFs cells. secreted from cells typically activate resident acquire myofibroblastic phenotype, while diffused by CAFs, turn, substantially increase progression BC. This review summarizes latest findings highlight functional role EV especially miRNAs, regulatory network. A better understanding EV-mediated cell-cell interactions crucial achieving effective treatment patients with

Language: Английский

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Extracellular Vesicle lncRNAs as Key Biomolecules for Cell-to-Cell Communication and Circulating Cancer Biomarkers

Non-Coding RNA, Journal Year: 2024, Volume and Issue: 10(6), P. 54 - 54

Published: Nov. 5, 2024

Extracellular vesicles (EVs) are secreted by almost every cell type and considered carriers of active biomolecules, such as nucleic acids, proteins, lipids. Their content can be uptaken released into the cytoplasm recipient cells, thereby inducing gene reprogramming phenotypic changes in acceptor cells. Whether effects EVs on physiology cells mediated individual biomolecules or collective outcome total transferred EV is still under debate. The RNA consists several types RNA, messenger (mRNA), microRNA (miRNA), long non-coding (lncRNA), latter defined transcripts longer than 200 nucleotides that do not code for proteins but have important established biological functions. This review aims to update our insights functional roles their cargo during cancer progression, highlight utility novel diagnostic prognostic biomarkers cancer, tackle technological advances limitations identification, integrity assessment, preservation its functionality.

Language: Английский

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Long non-coding RNAs are involved in the crosstalk between cancer-associated fibroblasts and tumor cells

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 9, 2024

The proliferation of tumors is not merely self-regulated by the cancer cells but also intrinsically connected to tumor microenvironment (TME). Within this complex TME, cancer-associated fibroblasts (CAFs) are pivotal in modulation onset and progression. Rich signaling interactions exist between CAFs cells, which crucial for regulation. Long non-coding RNAs (LncRNAs) emerge from cellular transcription as a class functionally diverse RNA molecules. Recent studies have revealed that LncRNAs integral crosstalk with capacity modify transcriptional activity secretion profiles, thus facilitating activation, proliferation, metastasis, drug resistance, other related functionalities. This comprehensive review revisits latest research on LncRNA-mediated encapsulates biological roles LncRNAs, delves into molecular pathways broader perspective, aspiring offer novel perspectives deeper comprehension etiology enhancement therapeutic approaches.

Language: Английский

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