The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 18, 2025

The mechanical properties of the tumor microenvironment (TME) undergo significant changes during growth, primarily driven by alterations in extracellular (ECM) stiffness and viscoelasticity. These not only promote progression but also hinder therapeutic efficacy impairing drug delivery activating mechanotransduction pathways that regulate crucial cellular processes such as migration, proliferation, resistance to therapy. In this review, we examine mechanisms through which cells sense transmit signals maintain homeostasis biomechanically altered TME. We explore current computational modelling strategies for pathways, highlighting need developing models incorporate additional components mechanosignaling machinery. Furthermore, review available methods measuring tumors clinical settings aiming at restoring TME blocking deregulated pathways. Finally, propose proper characterization a deeper understanding landscape TME, both tissue levels, are essential account influence forces on treatment efficacy.

Language: Английский

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Macrophages as a Potential Immunotherapeutic Target in Solid Cancers

Vaccines, Journal Year: 2022, Volume and Issue: 11(1), P. 55 - 55

Published: Dec. 26, 2022

The revolution in cancer immunotherapy over the last few decades has resulted a paradigm shift clinical care of cancer. Most immunotherapeutic regimens approved so far have relied on modulating adaptive immune system. In recent years, strategies and approaches targeting components innate immunity become widely recognized for their efficacy solid cancers. Macrophages are effector cells system, which can play crucial role generation anti-tumor through ability to phagocytose present tumor antigens immunity. However, macrophages that recruited microenvironment predominantly pro-tumorigenic roles. Several functions harnessing anti-tumorigenic properties shown promising results preclinical studies, them also advanced trials. this review, we comprehensive overview pathobiology TAMs progression malignancies. We discuss various mechanisms promote progression, such as inflammation, genomic instability, growth, stem cell formation, angiogenesis, EMT metastasis, tissue remodeling, immunosuppression, etc. addition, potential therapeutic explore how be used tool next-generation treatment

Language: Английский

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Inhibition of bladder cancer growth with homoharringtonine by inactivating integrin α5/β1-FAK/Src axis: A novel strategy for drug application

Pharmacological Research, Journal Year: 2023, Volume and Issue: 188, P. 106654 - 106654

Published: Jan. 11, 2023

The application of immune checkpoint inhibitors and FGFR protein tyrosine kinase have made a tremendous breakthrough in bladder cancer therapy. However, inadequate drug responses resistance interfere with successful treatment outcomes. For new to enter the market, there is long development cycle high costs low success rates. Repurposing previously Food Drug Administration (FDA)-approved medications using novel discovery strategies may be an optimal approach. Homoharringtonine (HHT) has been used for hematologic malignancies over 40 years China was approved by FDA approximately 10 ago. Many studies demonstrated that HHT effectively inhibits several types solid tumors, although underlying mechanisms action are unclear. In this study, we investigated activity against growth. We first compared HTT drugs currently clinically treatment. showed stronger inhibitory than cisplatin, carboplatin, doxorubicin. Our vitro vivo data inhibited proliferation, colony formation, migration, cell adhesion cells induced apoptosis arrest nanomolar concentration range. Furthermore, revealed could downregulate MAPK/Erk PI3k/Akt signaling pathways inactivating integrin α5/β1-FAK/Src axis. HHT-induced reduced cell-ECM interactions thus suppressing tumor metastasis progression. Altogether, shows enormous potential as anticancer agent applied combination strategy cancer.

Language: Английский

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Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2309 - 2309

Published: April 14, 2023

Prostate cancer (PCa) is the second most frequent type of in men worldwide, with 288,300 new cases and 34,700 deaths estimated United States 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination these. In advanced cases, androgen-deprivation therapy (ADT) considered first-line therapy; however, PCa patients eventually progresses to castration-resistant prostate (CRPC) despite ADT. Nonetheless, transition from androgen-dependent androgen-independent tumors not yet fully understood. The physiological processes epithelial-to-non-epithelial (“mesenchymal”) (EMT) mesenchymal-to-epithelial (MET) are essential normal embryonic development; they have also been linked higher tumor grade, metastatic progression, treatment resistance. Due this association, EMT MET identified as important targets novel therapies, including CRPC. Here, we discuss transcriptional factors signaling pathways involved EMT, addition diagnostic prognostic biomarkers that these processes. We tackle various studies conducted bench bedside current landscape EMT-targeted therapies.

Language: Английский

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Oleic acid inhibits the migration and invasion of breast cancer cells with stemness characteristics through oxidative stress-mediated attenuation of the FAK/AKT/NF-κB pathway

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 116, P. 106224 - 106224

Published: May 1, 2024

Oleic acid, found in a variety of food sources, is beneficial to health. However, studies on its anticancer effects cancer stem cells resistant conventional treatments and the mechanisms underlying such are scarce. Here, we evaluated oleic acid against breast with stemness characteristics. inhibited proliferation stem-like more significantly than that their respective parental cells, reduced expression cell markers migration invasion propensity. It also repressed phosphorylation FAK, AKT, NF-κB, proteins involved invasion. acid-induced increase reactive oxygen species levels mediated inhibition FAK/AKT/NF-κB signaling axis. Our study demonstrates oxidative stress plays an important role inhibiting metastatic behavior characteristics relevant for management treatment-resistant cancer.

Language: Английский

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CSF2 upregulates CXCL3 expression in adipocytes to promote metastasis of breast cancer via the FAK signaling pathway

Journal of Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 15(4)

Published: April 1, 2023

Abstract Recent studies have demonstrated that cancer-associated adipocytes (CAAs) in the tumor microenvironment are involved malignant progression of breast cancer. However, underlying mechanism CAA formation and its effects on development cancer still unknown. Here, we show CSF2 is highly expressed both CAAs cells. promotes inflammatory phenotypic changes through Stat3 signaling pathway, leading to secretion multiple cytokines proteases, particularly C–X–C motif chemokine ligand 3 (CXCL3). Adipocyte-derived CXCL3 binds specific receptor CXCR2 cells activates FAK enhancing mesenchymal phenotype, migration, invasion In addition, a combination treatment targeting shows synergistic inhibitory effect adipocyte-induced lung metastasis mouse 4T1 vivo. These findings elucidate novel provide potential therapeutic strategy for metastasis.

Language: Английский

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Breast stiffness, a risk factor for cancer and the role of radiology for diagnosis

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

Published: Aug. 30, 2023

Abstract Over the last five decades, breast density has been associated with increased risk of developing cancer. Mammographically dense breasts are considered those belonging to heterogeneously breasts, and extremely subgroups according American College Radiology’s Breast Imaging Reporting Data System (BI-RADS). There is a statistically significant correlation between mammographic presence more glandular tissue alone. However, strength this weak. Although mechanisms driving density-related tumor initiation progression still unknown, there evidence suggesting that certain molecular pathways participating in epithelial-stromal interactions may play pivotal role deposition fibrillar collagen, matrix stiffness, cell migration favor carcinogenesis. This article describes these as potential “landscapers” for We also introduce term “Breast Compactness” reflect collagen on chest CT scan use stiffness measurements imaging biomarkers cancer screening stratification.

Language: Английский

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An arabinose-rich heteropolysaccharide isolated from Belamcanda chinensis (L.) DC treats liver cancer by targeting FAK and activating CD40

Carbohydrate Polymers, Journal Year: 2024, Volume and Issue: unknown, P. 121831 - 121831

Published: Jan. 1, 2024

Language: Английский

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Prospects of focal adhesion kinase inhibitors as a cancer therapy in preclinical and early phase study

Expert Opinion on Investigational Drugs, Journal Year: 2024, Volume and Issue: 33(6), P. 639 - 651

Published: April 27, 2024

FAK, a nonreceptor cytoplasmic tyrosine kinase, plays crucial role in tumor metastasis, drug resistance, stem cell maintenance, and regulation of the microenvironment. FAK has emerged as promising target for therapy based on both preclinical clinical data.

Language: Английский

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Exploring the Therapeutic Potential of Focal Adhesion Kinase Inhibition in Overcoming Chemoresistance in Pancreatic Ductal Adenocarcinoma

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(3), P. 271 - 289

Published: Jan. 25, 2024

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related deaths worldwide. Focal adhesion kinase (FAK) a nonreceptor tyrosine often overexpressed in PDAC. FAK has been linked to cell migration, survival, proliferation, angiogenesis and adhesion. This review first highlights chemoresistant nature Second, role PDAC cancer progression resistance carefully described. Additionally, it discusses recent developments inhibitors as valuable drugs treatment PDAC, with focus on diamine-substituted-2,4-pyrimidine-based compounds, which represent most potent class clinical trials for disease. To conclude, relevant computational studies performed are reported highlight key structural features required interaction protein, aim optimizing this novel targeted therapy.

Language: Английский

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