The Interplay between Extracellular Matrix Remodeling and Cancer Therapeutics

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(8), P. 1375 - 1388

Published: Aug. 2, 2024

Abstract The extracellular matrix (ECM) is an abundant noncellular component of most solid tumors known to support tumor progression and metastasis. interplay between the ECM cancer therapeutics opens up new avenues in understanding biology. While protect from anticancer agents by serving as a biomechanical barrier, emerging studies show that various therapies induce remodeling, resulting therapy resistance progression. This review discusses critical issues this field including how influences treatment outcome, affect challenges associated with targeting ECM. Significance: intricate relationship reveals novel insights into biology its effective treatment. may anti-cancer agents, recent research highlights paradoxical role therapy-induced remodeling promoting explores key aspects therapeutics.

Language: Английский

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Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Language: Английский

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Cancer-associated Fibroblast–specific Expression of the Matricellular Protein CCN1 Coordinates Neovascularization and Stroma Deposition in Melanoma Metastasis

Cancer Research Communications, Journal Year: 2024, Volume and Issue: 4(2), P. 556 - 570

Published: Feb. 16, 2024

Melanoma is the leading cause of skin cancer-related death. As prognosis patients with melanoma remains problematic, identification new therapeutic targets essential. Matricellular proteins are nonstructural extracellular matrix proteins. They secreted into tumor microenvironment to coordinate behavior among different cell types, yet their contribution underinvestigated. Examples matricellular include those comprising CCN family. The family member, CCN1, highly proangiogenic. Herein, we show that, in human melanoma, although found several CCN1 expressed by a subset cancer-associated fibroblasts (CAF) and this expression correlates positively proangiogenic genes progressive disease/resistance anti-PD1 checkpoint inhibitors. Consistent these observations, syngeneic C57BL6 mouse model loss from Col1A2-Cre-, herein identified as "universal," fibroblasts, impaired metastasis subcutaneously injected B16F10 cells lung, concomitant disrupted neovascularization collagen organization. Disruption was validated using novel artificial intelligence-based image analysis platform that revealed significantly decreased phenotypic fibrosis composite morphometric scores. drug resistance linked deposition neoangiogenesis, data suggest due its multifaceted role, may represent target for drug-resistant melanoma. Our further emphasize essential role cancer-associated, (universal) Col1A2-Cre-fibroblasts remodeling play coordinating types within microenvironment.

Language: Английский

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Tenascin-C targeting strategies in cancer

Matrix Biology, Journal Year: 2024, Volume and Issue: 130, P. 1 - 19

Published: April 18, 2024

Language: Английский

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Prediction of tumor regression grade in far-advanced gastric cancer after preoperative immuno-chemotherapy using dual-energy CT-derived extracellular volume fraction

European Radiology, Journal Year: 2024, Volume and Issue: 35(1), P. 93 - 104

Published: July 9, 2024

Language: Английский

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Focus on mechano-immunology: new direction in cancer treatment

International Journal of Surgery, Journal Year: 2025, Volume and Issue: 111(3), P. 2590 - 2602

Published: Jan. 7, 2025

The immune response is modulated by a diverse array of signals within the tissue microenvironment, encompassing biochemical factors, mechanical forces, and pressures from adjacent tissues. Furthermore, extracellular matrix its constituents significantly influence function cells. In case carcinogenesis, changes in biophysical properties tissues can impact received cells, these c1an be translated into through mechano-transduction pathways. These pathways have profound on cellular functions, influencing processes such as cell activation, metabolism, proliferation, migration, etc. Tissue mechanics may undergo temporal during process offering potential for novel dynamic levels regulation. Here, we review advances mechanoimmunology malignancy studies, focusing how mechanosignals modulate behaviors cells at level, thereby triggering an that ultimately influences development progression malignant tumors. Additionally, also focused mechano-immunoengineering systems, with help which could to further understand tumor or alterations microenvironment provide new research directions overcoming immunotherapeutic resistance

Language: Английский

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Extracellular matrix cancer‐associated fibroblasts promote stromal fibrosis and immune exclusion in triple‐negative breast cancer

The Journal of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

The impact of high heterogeneity cancer-associated fibroblasts (CAFs) on triple-negative breast cancer (TNBC) immunotherapy response has not been fully elucidated, restricting progress in precision immuno-oncology. We integrated single-cell transcriptomic data from 18 TNBC patients and analyzed fibroblast subpopulations. Extracellular matrix CAFs (ecmCAFs) were identified as a subpopulation with distinct ECM-associated characteristics. ecmCAFs significantly enriched residual disease after neoadjuvant contributed to fibrotic tumor microenvironment T-cell exclusion. Secreted phosphoprotein 1 (SPP1) positive macrophages (SPP1+ Mφs) closely localized produced more transforming growth factor beta (TGFB1), interleukin (IL1B), SPP1 under hypoxic conditions. SPP1+ Mφs found facilitate the differentiation normal ecmCAFs, thus promoting ECM remodeling stromal fibrosis. Our work revealed critical role generating desmoplastic architecture driving immunosuppression TNBC. © 2025 Pathological Society Great Britain Ireland.

Language: Английский

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Discovering biomarkers associated with infiltration of CD8+ T cells and tumor-associated fibrosis in colon adenocarcinoma using single-cell RNA sequencing and gene co-expression network

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

Published: March 31, 2025

Background Colorectal adenocarcinoma (COAD) is a prevalent malignant tumor associated with high mortality rate. Within the microenvironment, CD8 + T cells play pivotal role in anti-tumor immune response within human body. Fibrosis directly and indirectly affects therapeutic of immunotherapy. However, significance regulatory genes tumor-associated fibrosis cell infiltration remains uncertain. Therefore, it imperative to identify biomarkers prognostic value elucidate precise fibrosis. Methods We performed single-cell transcriptome analysis COAD samples from GEO database. To evaluate samples, we utilized CIBERSORT ESTIMATE. Furthermore, analyzed correlation between infiltration. analyze expression’s quantitative composition data, conducted Weighted Gene Correlation Network Analysis deconvolution algorithm. The data for these analyses were obtained univariate Cox regression LASSO create model. predictive model was assessed through Kaplan-Meier analysis, survival prediction nomogram created. Additionally, chemotherapy drug sensitivity. estimate expression hub genes, employed immunohistochemistry, real-time PCR, western blot techniques. Results Single-cell has indicated higher prevalence samples. connection further confirmed by WGCNA using Protein-Protein Interaction network revealed three genes: LARS2 , SEZ6L2 SOX7 . A subsequently created COX regression, which included genes. Two ( ) found be upregulated lines tissues, while observed downregulated. demonstrated significant association cells, suggesting that could serve as potential targets gene therapy treating COAD. Conclusion This study identified key prognosis COAD, providing new diagnosing

Language: Английский

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A first-in-class inhibitor of homologous recombination DNA repair counteracts tumour growth, metastasis and therapeutic resistance in pancreatic cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: April 24, 2025

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is among the cancer types with poorest prognosis and survival rates primarily due to resistance standard-of-care therapies, including gemcitabine (GEM) olaparib. Particularly, wild-type (wt)BRCA tumours, most prevalent in PDAC, are more resistant DNA-targeting agents like olaparib, restraining their clinical application. Recently, we disclosed a monoterpene indole alkaloid derivative (BBIT20) as new inhibitor of homologous recombination (HR) DNA repair anticancer activity breast ovarian cancer. Since inhibition enhances sensitivity cells chemotherapy, aimed investigate potential BBIT20 against particularly carrying wtBRCA. Methods In vitro vivo PDAC models, human cell lines (including GEM-resistant cells), patient-derived organoids xenograft mice were used evaluate BBIT20, alone combination GEM or Disruption BRCA1-BARD1 interaction by was assessed co-immunoprecipitation, immunofluorescence yeast two-hybrid assay. Results The potent antiproliferative superior demonstrated regardless BRCA status, inducing cycle arrest, apoptosis, damage, while downregulating HR. disruption double-strand breaks further reinforced non-homologous end joining (NHEJ) suppression. heterodimer confirmed cells, showed antiproliferative, anti-migratory anti-invasive activity, overcoming inhibiting multidrug P-glycoprotein, upregulating intracellular GEM-transporter ENT1, resistance-related microRNA-20a metabolism enzymes RRM1/2. Furthermore, did not induce cells. It inhibited growth organoids, repressing HR, potentiating olaparib cytotoxicity. enhancement antitumor PDAC. Notably, it hindered tumour liver metastasis formation, improving orthotopic its stroma-targeting agent, reducing fibrotic extracellular matrix desmoplasia, associated an immune response depleting PD-L1 expression tissues, renders even appealing for therapy, immunotherapy. Conclusion These findings underscore great novel multifaceted drug candidate treatment.

Language: Английский

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Neoadjuvant Therapy for Mucosal Head and Neck Squamous Cell Carcinoma

JAMA Otolaryngology–Head & Neck Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Importance While neoadjuvant chemotherapy for head and neck squamous cell carcinoma dates to the earliest multidisciplinary approaches, introduction of immune checkpoint inhibitors (ICIs) has renewed enthusiasm research into its use. Although therapy remained mostly investigative through single-institutional clinical trials mucosal carcinoma, new data have emerged support Observations A narrative review was conducted by American Head Neck Society address current literature, evolving research, gaps in knowledge surrounding therapy. Neoadjuvant ICIs, most notably agents targeting anti–programmed death protein 1 (anti–PD-1), are a promising approach bolstering antitumor immunity prior ablating local structures. may allow an individualized approach, biomarkers guide patient selection limited. Potential benefits include de-escalation subsequent treatment, but curable disease also carries small real risk progression compromise curative options. Measures response pathologic, clinical, radiographic, there rapidly expanding capabilities diagnostics, such as circulating tumor DNA, with emerging potential provide objective quantification burden. Further strategies adaptive therapy, treatment selection/bioselection or modification surgery, adjuvant definitive treatment. ICI summarized this review. Optimized trial designs additional needed standardize surrogate outcomes compare survival standard Conclusions Relevance can be effective option precision oncology bolstered advent anti–PD-1 immunotherapy. However, tools predicting assessing remain evaluating strategies, combinations increase efficacy, comparisons approaches.

Language: Английский

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