Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 11, 2023

The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation distant metastasis. Anticancer treatments including adjuvant therapies targeted are effective in eliminating cancer cells but limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role development through changes macromolecule components, degradation enzymes stiffness. These variations under control cellular components tissue via aberrant activation signaling pathways, interaction ECM to multiple surface receptors, mechanical impact. Additionally, shaped regulates immune which results suppressive microenvironment hinders efficacy immunotherapies. Thus, acts as barrier protect from supports progression. Nevertheless, profound regulatory network remodeling hampers design individualized antitumor treatment. Here, we elaborate on composition ECM, discuss specific mechanisms remodeling. Precisely, highlight impact development, proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, escape. Finally, emphasize "normalization" potential strategy for anti-malignant

Language: Английский

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Tumor microenvironment: barrier or opportunity towards effective cancer therapy

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Oct. 17, 2022

Abstract Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis tumor. With the advent 3D culture advanced bioinformatic methodologies, it now possible to study TME’s individual components their interplay at higher resolution. Deeper understanding immune cell’s diversity, stromal constituents, repertoire profiling, neoantigen prediction TMEs has provided opportunity explore spatial temporal regulation therapeutic interventions. The variation TME composition among patients plays an important role in determining responders non-responders towards cancer immunotherapy. Therefore, there could be possibility reprogramming overcome widely prevailing issue immunotherapeutic resistance. focus present review understand complexity comprehending future perspective its as potential targets. later part describes sophisticated models emerging valuable means extensive account tools profile predict neoantigens. Overall, this provides comprehensive current knowledge available target TME.

Language: Английский

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Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 7, 2023

Since their invention in the early 2000s, tyrosine kinase inhibitors (TKIs) have gained prominence as most effective pathway-directed anti-cancer agents. TKIs shown significant utility treatment of multiple hematological malignancies and solid tumors, including chronic myelogenous leukemia, non-small cell lung cancers, gastrointestinal stromal HER2-positive breast cancers. Given widespread applications, an increasing frequency TKI-induced adverse effects has been reported. Although are known to affect organs body lungs, liver, tract, kidneys, thyroid, blood, skin, cardiac involvement accounts for some serious complications. The frequently reported cardiovascular side range from hypertension, atrial fibrillation, reduced function, heart failure sudden death. potential mechanisms these unclear, leading critical knowledge gaps development therapy guidelines. There limited data infer best clinical approaches detection therapeutic modulation effects, universal consensus regarding various management guidelines is yet be reached. In this state-of-the-art review, we examine pre-clinical studies curate evidence on pathophysiology, mechanisms, reactions. We expect that review will provide researchers allied healthcare providers with up-to-date information natural history, risk stratification, emerging cancer patients.

Language: Английский

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Targeting the tumor stroma for cancer therapy

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

Published: Nov. 2, 2022

Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part the tumor microenvironment, stroma is highly dynamic, heterogeneous commonly tumor-type specific, it mainly includes noncellular compositions such as extracellular matrix unique cancer-associated vascular system well a wide variety cellular components including activated fibroblasts, mesenchymal cells, pericytes. All these elements operate with each other in coordinated fashion collectively promote initiation, progression, metastasis therapeutic resistance. Over past few decades, numerous studies have been conducted to study interaction crosstalk between neoplastic cells. Meanwhile, we also witnessed exponential increase investigation recognition critical roles solid tumors. A series clinical trials targeting launched continually. In this review, introduce discuss current advances understanding various their cancers. We elaborate on potential novel approaches for tumor-stroma-based targeting, aim leap from bench bedside.

Language: Английский

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Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

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TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Sept. 17, 2022

Abstract Transforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as tumor suppressor the early stages but promoter late of cancer. Once cells are generated, TGF-β is responsible for orchestration immunosuppressive microenvironment (TME) supports growth, invasion, metastasis, recurrence, therapy resistance. These progressive behaviors driven by an “engine” metabolic reprogramming Recent studies have revealed that regulates driver (TMME). Intriguingly, ligands act “endocrine” cytokine influence host metabolism. Therefore, having insight into TMME instrumental acknowledging its wide range effects designing new treatment strategies. Herein, we try to illustrate concise definition based on published literature. Then, review elaborate contribution rewiring at cellular (intracellular), tissular (intercellular), organismal (cancer-host) levels. Furthermore, propose three potential applications targeting TGF-β-dependent mechanism reprogramming, paving way TGF-β-related antitumor from perspective

Language: Английский

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Cancer-associated fibroblasts: Origin, function, imaging, and therapeutic targeting

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 189, P. 114504 - 114504

Published: Aug. 23, 2022

Language: Английский

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STAT3 pathway in cancers: Past, present, and future

MedComm, Journal Year: 2022, Volume and Issue: 3(2)

Published: March 23, 2022

Abstract Signal transducer and activator of transcription 3 (STAT3), a member the STAT family, discovered in cytoplasm almost all types mammalian cells, plays significant role biological functions. The duration STAT3 activation normal tissues is transient event strictly regulated. However, cancer tissues, activated an aberrant manner induced by certain cytokines. continuous regulates expression downstream proteins associated with formation, progression, metastasis cancers. Thus, elucidating mechanisms regulation designing inhibitors targeting pathway are considered promising strategies for treatment. This review aims to introduce history, research advances, prospects concerning cancer. We consequent hallmarks tumor biology that pathway. Moreover, we summarize emerging development target novel drug delivery systems delivering these inhibitors. barriers against pathway, focus future on targets our perspective overall utility treatment also discussed.

Language: Английский

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Chronic inflammation, cancer development and immunotherapy

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 14, 2022

Chronic inflammation plays a pivotal role in cancer development. Cancer cells interact with adjacent cellular components (pro-inflammatory cells, intrinsic immune stromal etc.) and non-cellular to form the inflammatory tumor microenvironment (TME). Interleukin 6 (IL-6), macrophage migration inhibitory factor (MIF), checkpoint factors other pro-inflammatory cytokines produced by TME are main mediators of intercellular communication TME, which link chronic stimulating different oncogenic signaling pathways improving escape promote In parallel, ability monocytes, T regulatory (Tregs) B (Bregs) perform homeostatic tolerogenic functions is hijacked leading local or systemic immunosuppression. Standard treatments for advanced malignancies such as chemotherapy radiotherapy have improved last decades. However, clinical outcomes certain malignant cancers not satisfactory due drug resistance side effects. The application therapy (ICT) has brought hope treatment, although therapeutic efficacy still limited immunosuppressive microenvironment. Emerging evidences reveal that ideal therapies including clearance disruption tumor-induced immunosuppression targeting suppressive well reactivation anti-tumor ICT. Here, we review impacts major their downstream molecules on We also discuss important management cancer.

Language: Английский

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Cancer stem cells: advances in knowledge and implications for cancer therapy

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

Published: July 5, 2024

Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.

Language: Английский

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