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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Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 71 - 71

Published: Jan. 6, 2025

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes suppressor genes transformed cells, significantly contributes to development at both primary distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues downstream signals, altering phenotype stromal cells immune cells. This remolds area surrounding ultimately fostering an immunosuppressive microenvironment. Therefore, correcting TME by targeting modifications holds substantial promise for cancer treatment. review synthesizes recent research that elucidates impact specific regulations-ranging from DNA methylation histone chromatin remodeling-on within TME. Notably, we highlight their functional roles either promoting or restricting We also discuss potential applications agents treatment, envisaging ability normalize ecosystem. aims assist researchers understanding dynamic interplay between epigenetics TME, paving way better therapy.

Language: Английский

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Formononetin Affects Polarization of M2 Macrophages Through the Jak2/Stat3 Pathway in Hcc

Published: Jan. 1, 2025

Language: Английский

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Single-cell RNA sequencing reveals cellular and molecular heterogeneity in extensive-stage small cell lung cancer with different chemotherapy responses

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 21, 2025

Despite its rapid growth and early metastasis, small cell lung cancer (SCLC) is more chemosensitive than other cancers. However, some patients with extensive-stage SCLC (ES-SCLC) do not respond to first-line chemotherapy, resulting in poorer prognoses due inter- intratumoral heterogeneity. In this study, we conducted single-cell RNA sequencing of 9 treatment-naive ES-SCLC samples. Based on comprehensive imaging evidence collected before after two cycles chemotherapy sample types, the samples were categorized into three groups: progressive disease pleural effusion (PD_PE group, n = 1), primary tumor (PD_TU 2), partial response (PR_TU 6). transcriptomic landscape type composition, PD represent a multicellular ecosystem distinct from PR The immune response, along elevated expression immune-related genes such as LTF, SLPI, SPARC IGLV1-51, might correlate poor ES-SCLC. We also observed that T cells, particularly effector abundant PD_TU TNFA signaling via NFκB being significantly enriched. group was strongly enriched macrophages tumor-associated (TAMs), angiogenesis TAMs highly Immunomodulatory fibroblasts pathways epithelial-mesenchymal transition upregulated. This study offers first insights cellular molecular heterogeneity different responses.

Language: Английский

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Mechano-mediated M2 macrophage polarization and immune suppression in stiffened tumor microenvironment

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Abstract The tumor microenvironment (TME), which is composed of various cell types and the extracellular matrix (ECM), plays crucial roles in cancer progression treatment outcomes. However, impact mechanical properties ECM, specifically collagen fibril alignment crosslinking, on macrophage behavior polarization less understood. To investigate this, we reconstituted 3D matrices to mimic physical characteristics TME. Our results demonstrated that stiffening through or crosslinking fibrils promotes toward anti-inflammatory M2 phenotype. This phenotype characterized by increased expression CD105 CD206 a distinct cytokine secretion profile. stiffness aligned activate mechanotransduction pathways, notably integrin β1 PI3K signaling, leading IL-4 secretion, acts an autocrine manner further promote polarization. Interestingly, these stiffened microenvironments also suppressed proinflammatory response. In coculture experiments with breast lines (MDA-MB-231 MCF-7), macrophages within significantly proliferation invasion. These findings suggest its create more favorable environment for modulating activity. Overall, our study underscores critical role ECM mechanics shaping immune TME, highlighting potential therapies target inhibit enhance efficacy.

Language: Английский

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PPIC-labeled CAFs: Key players in neoadjuvant chemotherapy resistance for gastric cancer

Translational Oncology, Journal Year: 2024, Volume and Issue: 48, P. 102080 - 102080

Published: Aug. 7, 2024

Gastric cancer (GC) is the fourth leading cause of deaths, with advanced cases having a median survival less than one year. Neoadjuvant chemotherapy (NCT) vital but faces drug resistance issues, partly due to cancer-associated fibroblasts (CAFs). Yet, specific CAF subpopulations contributing are poorly understood.

Language: Английский

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