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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Modulation of the Neuro–Cancer Connection by Metabolites of Gut Microbiota

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 270 - 270

Published: Feb. 12, 2025

The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, cancer progression. Recent advances have accentuated significant role of microbiota metabolites in modulating systemic processes that influence both brain health tumorigenesis. This paper explores emerging concept metabolite-mediated modulation within connection, focusing on key such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, lipopolysaccharides (LPS). While microbiota's impact immune regulation, neuroinflammation, tumor development is well established, gaps remain grasping how specific contribute to neuro-cancer interactions. We discuss with potential implications for neurobiology cancer, indoles polyamines, which yet be extensively studied. Furthermore, we review preclinical clinical evidence linking dysbiosis, altered metabolite profiles, tumors, showcasing limitations research gaps, particularly human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal transplantation, probiotics, demonstrate promise but also indicate hurdles translating these findings therapies. concludes call standardized multi-omics approaches bi-directional frameworks integrating microbiome, neuroscience, oncology develop personalized therapeutic strategies patients.

Language: Английский

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Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment

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

Published: Feb. 14, 2025

Metabolic reprogramming is one of the major biological features malignant tumors, playing a crucial role in initiation and progression cancer. The tumor microenvironment consists various non-cancer cells, such as hepatic stellate cancer-associated fibroblasts (CAFs), immune well extracellular matrix soluble substances. In liver cancer, metabolic not only affects its own growth survival but also interacts with other cells by influencing expression release metabolites cytokines (such lactate, PGE2, arginine). This interaction leads to acidification restricts uptake nutrients resulting competition symbiosis. At same time, neighboring during proliferation differentiation processes impacts immunity. article provides comprehensive overview crosstalk between cancer their microenvironment, deepening our understanding relevant findings pathways. contributes further regulation development evasion mechanisms while providing assistance advancing personalized therapies targeting pathways for anti-cancer treatment.

Language: Английский

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Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 90 - 90

Published: Jan. 31, 2025

Chimeric antigen receptor-T (CAR-T) cell therapy has demonstrated impressive efficacy in the treatment of blood cancers; however, its effectiveness against solid tumors been significantly limited. The differences arise from a range difficulties linked to tumors, including an unfriendly tumor microenvironment, variability within and barriers CAR-T infiltration longevity at location. Research shows that reasons for decreased cells treating are not well understood, highlighting ongoing need strategies address these challenges. Current frequently incorporate combinatorial therapies designed boost functionality enhance their capacity effectively target tumors. However, remain testing phase necessitate additional validation assess potential benefits. CAR-NK (natural killer), CAR-iNKT (invariant natural killer T), CAR-M (macrophage) emerging as promising Recent studies highlight construction optimization cells, emphasizing overcome unique challenges posed by such hypoxia metabolic barriers. This review focuses on CAR

Language: Английский

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CNPY2 in Solid Tumors: Mechanisms, Biomarker Potential, and Therapeutic Implications

Biology, Journal Year: 2025, Volume and Issue: 14(2), P. 214 - 214

Published: Feb. 18, 2025

Canopy FGF signaling regulator 2 (CNPY2) has emerged as a crucial player in cancer development by promoting cell proliferation, tissue repair, and angiogenesis. This review synthesizes the current understanding of CNPY2's role solid tumors, particularly renal carcinoma, prostate cancer, hepatocellular non-small-cell lung cancer. CNPY2 modulates key pathways such p53, MYLIP, NF-κB, AKT/GSK3β, thereby driving tumor growth progression. In paradoxically promotes through p53 upregulation, while drives cycle progression via destabilization. it enhances stabilizing androgen receptors MYLIP interaction, contributes to chemoresistance metastasis NF-κB AKT/GSK3β signaling. Additionally, influences microenvironment, impacting immune function metastatic potential. As potential biomarker, shows promise for detection prognosis, when used combination with other markers. Early therapeutic strategies, including siRNA miRNA approaches, are under exploration, though challenges remain due expression normal tissues off-target effects. underscores need further research fully elucidate oncogenic mechanisms develop targeted therapies. Improved diverse roles may lead novel diagnostic approaches tumors.

Language: Английский

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Exploring the metabolic alterations in cervical cancer induced by HPV oncoproteins: From mechanisms to therapeutic targets

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189292 - 189292

Published: March 1, 2025

The role of human Papillomavirus (HPV) in metabolic reprogramming is implicated the development and progression cervical cancer. During carcinogenesis, cancer cells modify various pathways to generate energy sustain their growth development. Cervical cancer, one most prevalent malignancies affecting women globally, involves alterations such as increased glycolysis, elevated lactate production, lipid accumulation. oncoproteins, primarily E6 E7, which are encoded by high-risk HPVs, facilitate accumulation several markers, promoting not only but also metastasis, immune evasion, therapy resistance. HPV oncoproteins interact with cellular MYC (c-MYC), retinoblastoma protein (pRB), p53, hypoxia-inducible factor 1α (HIF-1α), leading induction favour Warburg effect. Metabolic enables persist for an extended period accelerates This review summarizes contributions Additionally, this provides insights into how opens avenues novel therapeutic strategies, including discovery new repurposed drugs that could be applied treat

Language: Английский

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Recent Exploration of Solid Cancer Biomarkers Hidden Within Urine or Blood Exosomes That Provide Fundamental Information for Future Cancer Diagnostics

Diagnostics, Journal Year: 2025, Volume and Issue: 15(5), P. 628 - 628

Published: March 5, 2025

Cancer cells exhibit abnormal behavior compared to normal cells. They ignore growth arrest signals such as contact inhibition, a mechanism that stops their proliferation when they collide with surrounding cells, and proliferate in an uncontrolled manner, destroying tissue. Early detection treatment of cancer are therefore important for healthy longevity. differ from characteristic gene expression due abnormalities. markers reflect these characteristics have been searched applied diagnosis. Although analysis blood antigens has the main method, further development diagnostic system is needed early cancer. Next-generation sequencers improved technology, making it possible analyze detailed nucleic acid molecules or urine. In addition, release extracellular vesicles, exosomes, which known contain may serve markers. This review summarizes latest findings on exosomal

Language: Английский

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Current advancement of immune function paradox of tumour-infiltrating cells and their immunotherapeutic targets: a mini-review

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

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Expanding the Therapeutic Reach of Chimeric Antigen Receptor T-Cells and Bispecific T-Cell Engagers Across Solid Tumors

JCO Precision Oncology, Journal Year: 2025, Volume and Issue: 9

Published: March 1, 2025

The introduction of T-cell–based therapeutics in hematologic malignancies has led to improvements outcomes for patients with acute leukemia, lymphoma, and multiple myeloma. To date, the Food Drug Administration (FDA) approved seven chimeric antigen receptor-T (CAR-T) cell therapies bispecific T-cell engagers (BiTEs) across a variety malignancies; however, extension CAR-T BiTEs solid tumor arena been somewhat limited. In this review, we discuss landmark data that commercialization four novel FDA-approved malignancies, including tarlatamab small lung cancer, afamitresgene autoleucel synovial sarcoma, lifileucel metastatic melanoma, tebentafusp uveal melanoma. We targetable landscape under investigation malignancies. explore translational potential various CARs active investigation, human epidermal growth factor receptor 2–directed breast prostate stem antigen–directed (EGFR)-IL13Ra2 EGFR-vIII glioblastoma, GD2-directed neuroblastoma. glean from lessons learned existing emphasize solutions toward facilitating clinical rollout tumors, scalability meet growing needs oncology. Some include addressing on-target, off-tumor toxicity; improving manufacturing CARs; optimizing tissue-specific microenvironment by combating immune desert tumors; discovering natural neoantigens non–self-epitopes generated tumor-specific mutations. These concepts can help provide transformative benefits coming years.

Language: Английский

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Harnessing Immune Rejuvenation: Advances in Overcoming T Cell Senescence and Exhaustion in Cancer Immunotherapy

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Immunotherapy has transformed the landscape of cancer treatment, with T cell-based strategies at forefront this revolution. However, durability these responses is frequently undermined by two intertwined phenomena: cell exhaustion and senescence. While driven chronic antigen exposure in immunosuppressive tumor microenvironment, leading to a reversible state diminished functionality, senescence reflects more permanent, age- or stress-induced arrest cellular proliferation effector capacity. Together, processes represent formidable barriers sustained anti-tumor immunity. In review, we dissect molecular underpinnings senescence, revealing how dysfunctions synergistically contribute immune evasion resistance across range solid tumors. We explore cutting-edge therapeutic approaches aimed rewiring exhausted senescent phenotypes. These include advances checkpoint blockade, engineering "armored" CAR-T cells, senolytic therapies that selectively eliminate novel interventions reinvigorate system's capacity for eradication. By spotlighting emerging target both provide forward-looking perspective on potential harness rejuvenation. This comprehensive review outlines next frontier immunotherapy: unlocking durable overcoming intrinsic aging exhaustion, ultimately paving way transformative breakthroughs.

Language: Английский

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