Emerging role of exosomes in cancer therapy: progress and challenges

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 13, 2025

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

Language: Английский

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Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

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Writers, readers, and erasers RNA modifications and drug resistance in cancer

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

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

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Inflammation and Immune Escape in Ovarian Cancer: Pathways and Therapeutic Opportunities

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 895 - 909

Published: Jan. 1, 2025

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, largely due to its late-stage diagnosis and high recurrence rates. Chronic inflammation is a critical driver OC progression, contributing immune evasion, tumor growth, metastasis. Inflammatory cytokines, including IL-6, TNF-α, IL-8, as well key signaling pathways such nuclear factor kappa B (NF-kB) signal transducer activator transcription 3 (STAT3), are upregulated in OC, promoting tumor-promoting environment. The microenvironment (TME) characterized by cells like tumor-associated macrophages (TAMs) regulatory T (Tregs), which suppress anti-tumor responses, facilitating evasion. Furthermore, utilize checkpoint pathways, PD-1/PD-L1, inhibit cytotoxic cell activity. Targeting these inflammatory evasion mechanisms offers promising therapeutic strategies. COX-2 inhibitors, Janus kinase/signal (JAK/STAT) pathway blockers, NF-kB inhibitors have shown potential preclinical studies, while targeting PD-1/PD-L1 CTLA-4 been explored with mixed results OC. Additionally, emerging research on microbiome inflammation-related biomarkers, microRNAs (miRNAs) exosomes, points new opportunities for early detection precision medicine. Future approaches treatment must focus personalized strategies that target TME, integrating anti-inflammatory therapies immunotherapy enhance patient outcomes. Continued into interplay between essential developing effective, long-lasting treatments.

Language: Английский

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Unraveling the Role of Fusobacterium nucleatum in Colorectal Cancer: Molecular Mechanisms and Pathogenic Insights

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 368 - 368

Published: Jan. 23, 2025

Fusobacterium nucleatum, a gram-negative anaerobic bacterium, has emerged as significant player in colorectal cancer (CRC) pathogenesis. The bacterium causes persistent inflammatory reaction the mucosa by stimulating release of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α, creating an environment conducive to progression. F. nucleatum binds penetrates epithelial cells through adhesins such FadA, impairing cell junctions encouraging epithelial-to-mesenchymal transition (EMT), which is associated with advancement. Additionally, modulates host immune system, suppressing activity conditions favorable for tumor growth. Its interactions gut microbiome contribute dysbiosis, further influencing carcinogenic pathways. Evidence indicates that can inflict DNA damage either directly via reactive oxygen species or indirectly environment. it triggers oncogenic pathways, especially Wnt/β-catenin signaling pathway, promotes growth longevity. Moreover, alters microenvironment, impacting behavior, metastasis, therapeutic responses. purpose this review elucidate molecular mechanisms contributes CRC. Understanding these crucial development targeted therapies diagnostic strategies CRC nucleatum.

Language: Английский

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Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

Cancer stem cells (CSCs) are a small subset within the tumor mass significantly contributing to cancer progression through dysregulation of various oncogenic pathways, driving growth, chemoresistance and metastasis formation. The aggressive behavior CSCs is guided by several intracellular signaling pathways such as WNT, NF-kappa-B, NOTCH, Hedgehog, JAK-STAT, PI3K/AKT1/MTOR, TGF/SMAD, PPAR MAPK kinases, well extracellular vesicles exosomes, molecules cytokines, chemokines, pro-angiogenetic growth factors, which finely regulate CSC phenotype. In this scenario, microenvironment (TME) key player in establishment permissive niche, where engage intricate communications with diverse immune cells. "oncogenic" mainly represented B T lymphocytes, NK cells, dendritic Among macrophages exhibit more plastic adaptable phenotype due their different subpopulations, characterized both immunosuppressive inflammatory phenotypes. Specifically, tumor-associated (TAMs) create an milieu production plethora paracrine factors (IL-6, IL-12, TNF-alpha, TGF-beta, CCL1, CCL18) promoting acquisition stem-like, invasive metastatic TAMs have demonstrated ability communicate via direct ligand/receptor (such CD90/CD11b, LSECtin/BTN3A3, EPHA4/Ephrin) interaction. On other hand, exhibited capacity influence creating favorable for progression. Interestingly, bidirectional TME leads epigenetic reprogramming sustains malignant transformation. Nowadays, integration biological computational data obtained cutting-edge technologies (single-cell RNA sequencing, spatial transcriptomics, trajectory analysis) has improved comprehension biunivocal multicellular dialogue, providing comprehensive view heterogeneity dynamics CSCs, uncovering alternative mechanisms evasion therapeutic resistance. Moreover, combination biology will lead development innovative target therapies dampening CSC-TME Here, we aim elucidate most recent insights on complex interactions specifically TAMs, tracing exhaustive scenario from primary

Language: Английский

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mRNA vaccine platforms: linking infectious disease prevention and cancer immunotherapy

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: March 12, 2025

The advent of mRNA vaccines, accelerated by the global response to COVID-19 pandemic, marks a transformative shift in vaccine technology. In this article, we discuss development, current applications, and prospects vaccines for both prevention treatment infectious diseases oncology. By leveraging capacity encode antigens within host cells directly, provide versatile scalable platform suitable addressing broad spectrum pathogens tumor-specific antigens. We highlight recent advancements design, innovative delivery mechanisms, ongoing clinical trials, with particular emphasis on their efficacy combating diseases, such as COVID-19, Zika, influenza, well emerging potential cancer immunotherapy. also address critical challenges, including stability, optimization immune responses, broader issue accessibility. Finally, review strategies advancing next-generation aim overcoming limitations technology enhancing preventive therapeutic approaches oncological diseases.

Language: Английский

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Microenvironment-based immunotherapy in oral cancer: a comprehensive review

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(5)

Published: March 28, 2025

Language: Английский

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Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy

Nutrients, Journal Year: 2024, Volume and Issue: 16(21), P. 3741 - 3741

Published: Oct. 31, 2024

Conventional cancer treatments include surgical resection, chemotherapy, hyperthermia, immunotherapy, hormone therapy, and locally targeted therapies such as radiation therapy. Standard often require the use of multiple agents, which can activate nuclear factor kappa B (NF-κB) in tumor cells, leading to reduced cell death increased drug resistance. Moreover, agents also contributes added toxicity, resulting poor treatment outcomes. Cancer cells gradually develop resistance almost all chemotherapeutics through various mechanisms, efflux, alterations metabolism transport, changes signal transduction pathways, enhanced DNA repair capacity, evasion apoptosis, mutations, reactivation targets, interaction with microenvironment, cell-stroma interactions, epithelial–mesenchymal transition (EMT)-mediated chemoresistance, epigenetic modifications, metabolic alterations, effect stem (CSCs). Developing new strategies improve chemotherapy sensitivity while minimizing side effects is essential for achieving better therapeutic outcomes enhancing patients’ quality life. One promising approach involves combining conventional propolis its flavonoids. These natural compounds may enhance response reducing toxicity. Propolis components sensitize chemotherapeutic likely by inhibiting NF-κB activation, reprogramming tumor-associated macrophages (TAMs; an M2-like phenotype), thereby release matrix metalloproteinase (MMP)-9, cytokines, chemokines, vascular endothelial growth (VEGF). By TAMs, overcome EMT-mediated disrupt crosstalk between CSCs, inhibit maintenance stemness, reverse acquired immunosuppression, thus promoting antitumor mediated cytotoxic T-cells. This review highlights potential flavonoids modulate responsiveness modalities. The evidence suggests that novel incorporating could be developed positive cytotoxicity peripheral blood leukocytes, liver, kidney cells. Therefore, polyphenolic/flavonoid hold combination clinical types cancers.

Language: Английский

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Tumor‐associated macrophages: A sentinel of innate immune system in tumor microenvironment gone haywire

Cell Biology International, Journal Year: 2024, Volume and Issue: 48(10), P. 1406 - 1449

Published: July 25, 2024

The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising cancer-associated fibroblasts (CAF), immune cells, blood vessels, signaling molecules, TME often likened to soil supporting seed (tumor). Among its constituents, tumor-associated macrophages (TAMs) play pivotal role, exhibiting dual nature as both promoters inhibitors growth. This review explores intricate relationship between TAMs TME, emphasizing their diverse functions, from phagocytosis tissue repair modulating responses. plasticity highlighted, showcasing ability adopt either protumorigenic or anti-tumorigenic phenotypes based on environmental cues. In context cancer, TAMs' pro-tumorigenic activities include promoting angiogenesis, inhibiting responses, fostering metastasis. manuscript delves into therapeutic strategies targeting TAMs, challenges faced depleting due multifaceted roles. focus shifts towards reprogramming an M1-like phenotype, exploring interventions such interferons, checkpoint inhibitors, small molecule modulators. Noteworthy advancements use CSF1R CD40 agonists, CD47 blockade, demonstrating promising results preclinical clinical settings. A significant section dedicated Chimeric Antigen Receptor (CAR) technology (CAR-M cells). While CAR-T cells have shown success hematological malignancies, efficacy solid tumors has been limited. CAR-M engineered infiltrate tumors, are presented potential breakthrough, with development, challenges, outcomes. concludes exploration third-generation technology, offering insight in-vivo nonviral vector approaches. conclusion, understanding complex dynamic role cancer crucial for developing effective strategies. early-stage TAM-targeted therapies show promise, further extensive research larger trials warranted optimize improve overall

Language: Английский

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