Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123437 - 123437
Published: May 1, 2025
Language: Английский
Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 8, 2025
Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance gastrointestinal cancers (GI), particularly through pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth reshape TME, creating conditions such as nutrient depletion, hypoxia, acidity that impair antitumor immune responses. Immune TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes promote progression reduce efficacy therapies. The competition for essential nutrients, glucose, between cancer compromises functions effector cells, T cells. Additionally, by-products like lactate kynurenine further suppress activity populations, including regulatory M2 macrophages. Targeting glycolysis presents new opportunities overcome improve therapeutic outcomes GI cancers. Modulating these key has potential reinvigorate exhausted shift toward phenotypes, enhance effectiveness immunotherapies other treatments. Future strategies will require continued research into metabolism, development novel inhibitors, clinical trials evaluating combination Identifying validating biomarkers be crucial patient stratification treatment monitoring. Insights may have broader implications across multiple types, offering avenues improving treatment.
Language: Английский
Citations
1
Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 22, 2025
Cancer stem cells (CSCs), are a critical subpopulation within tumours, and defined by their capacity for self-renewal, differentiation, tumour initiation. These unique traits contribute to progression, metastasis, resistance conventional treatments like chemotherapy radiotherapy, often resulting in cancer recurrence poor patient outcomes. As such, CSCs have become focal points developing advanced therapies. This review highlights progress CSC-targeted treatments, including chimeric antigen receptor T-cell (CAR-T) therapy, immunotherapy, molecular targeting, nanoparticle-based drug delivery systems. Plant-derived compounds gene-editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR), explored potential enhance precision minimize side effects. Metabolic pathways integral CSC survival, mitochondrial dynamics, mitophagy (regulated dynamin-related protein 1 [DRP1] the PINK1/Parkin pathway), one-carbon metabolism, amino acid metabolism (involving enzymes glutaminase (GLS) glutamate dehydrogenase (GDH]), lipid hypoxia-induced metabolic reprogramming mediated hypoxia-inducible factors (HIF-1α HIF-2α), examined therapeutic targets. The adaptability of through autophagy, flexibility, epigenetic regulation metabolites α-ketoglutarate, succinate, fumarate is discussed. Additionally, extracellular vesicles nicotinamide adenine dinucleotide (NAD⁺) identified pivotal redox balance, DNA repair, modifications. Addressing challenges heterogeneity, immune evasion, treatment durability requires interdisciplinary collaboration. Advancing therapies essential overcoming preventing relapse, paving way transformative treatments. underscores importance leveraging innovative technologies fostering collaboration revolutionize treatment.
Language: Английский
Citations
1
Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217694 - 217694
Published: April 1, 2025
Language: Английский
Citations
1
Essays in Biochemistry, Journal Year: 2025, Volume and Issue: 69(02)
Published: March 7, 2025
The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a crucial component the host's innate immunity and plays central role in detecting cytosolic double-stranded DNA from endogenous exogenous sources. Upon activation, cGAS synthesizes cGAMP, which binds to STING, triggering cascade immune responses, including production type I interferons pro-inflammatory cytokines. In context cancers, cGAS-STING can exert dual roles: on one hand, it promotes anti-tumor by enhancing antigen presentation, stimulating T-cell inducing direct tumor cell apoptosis. On other chronic particularly tumors with chromosomal instability, lead suppression progression. Persistent signaling results up-regulation checkpoint molecules such as PD-L1, contributing evasion metastasis. Consequently, strategies targeting have consider balance activation tolerance caused activation. This review explores mechanisms underlying both protumor roles pathway, focus potential therapeutic approaches, challenges faced their clinical application, along corresponding solutions.
Language: Английский
Citations
0
Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
Language: Английский
Citations
0
Journal of Gastrointestinal Oncology, Journal Year: 2025, Volume and Issue: 16(2), P. 415 - 434
Published: April 1, 2025
Colorectal cancer (CRC) is a frequently diagnosed across the world and has increased in prevalence over last decade. This study aimed to assess biological roles, influences on radiosensitivity, possible molecular mechanism of Golgi phosphoprotein 3 (GOLPH3) CRC. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) were used examine GOLPH3 expression. In vivo vitro assays carried out clarify function The differentially expressed genes (DEGs) CRC cells with knockdown identified through RNA sequencing (RNA-seq). Based DEGs associated data from Cancer Genome Atlas (TCGA) database, pathways that could be regulated by predicted via Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis. CRC, was upregulated, upregulation predictive poor prognosis. inhibited cell proliferation, migration, invasion but promoted apoptosis reduced radiotherapy resistance. Conversely, overexpression, malignant behavior resistance enhanced. vivo, impeded tumor growth. Mechanistically, localization smoothened (SMO) membrane, thereby activating AMP-activated protein kinase (AMPK)-mediated glycolysis. Additionally, final product glycolysis, lactate, induced H3 lysine 18 lactylation (H3K18), which enriched promoter stimulate transcription GOLPH3. progression enhanced glycolysis mediated SMO-AMPK axis.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: May 14, 2025
Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy characterized by complex tumor microenvironment (TME) that plays pivotal role in initiation, progression, immune evasion. Recent advancements have highlighted the intricate interplay between infiltration patterns, checkpoint dysregulation, metabolic reprogramming driving HNSCC escape. Despite these insights, significant challenges remain, including incomplete understanding of specific evasion pathways lack personalized therapeutic strategies. To address gaps, this review introduces novel “Trinity” regulatory network HNSCC, encompassing: (1) reprogramming-mediated modulation, (2) stromal cell-driven dysfunction, (3) epigenetic remodeling fostering tolerance. This framework provides theoretical foundation for development multi-targeted combination therapies offers innovative strategies to overcome Additionally, systematically synthesizes current relationship escape, with focus on emerging immunotherapeutic approaches such as PD-1/PD-L1 inhibitors CAR-T therapy. Leveraging cutting-edge single-cell sequencing spatial transcriptomics, we elucidate spatiotemporal heterogeneity landscape propose new paradigm “lineage plasticity-driven adaptation.” These insights not only advance our biology but also pave way precision immunotherapies aimed at improving patient survival quality life. By integrating multidisciplinary perspectives, work underscores importance targeting TME achieve durable clinical responses immunotherapy resistance HNSCC.
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: May 22, 2025
Background Tumor metabolism reprogramming is a hallmark of cancer, but metabolite-mediated intercellular communication remains poorly understood. To address this gap, we estimated and explored events exploring based on single‐cell RNA data, to explore the metabolic landscape tumor microenvironment (TME) in lung adenocarcinoma (LUAD) identify novel metabolite signaling axis. Methods The scRNA-seq dataset was subjected dimensionality reduction using Seurat package. Cell annotation manually performed typical markers from Marker 2.0 previous studies. Single‐cell abundance were inferred MEBOCOST. TCGA‐LUAD datasets used estimate analyze immune cell infiltration levels hot score ESTIMATE ssGSEA algorithms. Additionally, survival analysis conducted genes within relative All above validated by two Gene Expression Omnibus (GEO) datasets. expression patterns PTGDR PTGDS RT‐qPCR fluorescence situ hybridisation. Results Five landmark metabolites across types identified as prostaglandin D2 (PGD2), D-Mannose, Choline, L-Cysteine, Cholesterol TME LUAD. Prostaglandin (PGD2) emerged key player, primarily produced fibroblasts plasmacytoid dendritic cells (pDCs) via gene mast HPGDS gene. PGD2 shown be received receptor ( ) NK/T transported SLCO2A1 transporter endothelial cells. CX3CR1+ cells, which are prominent cytotoxic populations, autocrine axis, involved signaling, while KLRC2+ NK, DNAJB1+ NK CD8+ MAIT participate paracrine signaling. may also assist lactate efflux clinical relevance axis multiple bulk datasets, showing that it associated with such linked better prognosis Furthermore, found risk model developed could predict responses therapy cold tumors, suggesting potential drugs benefit low-risk patients. These findings further supported RT-qPCR immunofluorescence confirmed downregulation LUAD tissues compared normal tissues. Conclusion Collectively, these results suggest its play significant role tumor-suppressive anti‐inflammatory effects LUAD, applications management decision‐making.
Language: Английский
Citations
0
BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)
Published: May 23, 2025
Bladder cancer (BCa), a prevalent malignancy of the urinary tract, is associated with high recurrence and mortality rates. SLC16A7, member solute carrier family 16 (SLC16), encodes monocarboxylate transporters that are involved in proton-coupled transport metabolites, including lactate, pyruvate, ketone bodies, across cell membranes. Evidence suggests SLC16A7 exhibits variable expression cancers may influence tumor development, progression, immune regulation. This study examined role prognosis, regulation, focusing on BCa. A comprehensive analysis was conducted to evaluate clinical immunological relevance multiple types using data from 33 datasets 'The Cancer Genome Atlas (TCGA). ' Associations between clinicopathological features, prognostic indicators, mutation burden (TMB), microsatellite instability (MSI), infiltration, immune-related gene were systematically analyzed. Experimental validation performed assess BCa tissues lines. The value confirmed follow-up an independent patient cohort. Functional studies included proliferation assays investigate effect SLC16A7. CD8 + T cells obtained peripheral blood healthy donors stimulated CD3 CD28 antibodies combination recombinant IL-2. To co-culture experiments activated cells. Additionally, chemotaxis ELISA analyses responses mediated by downregulated types, BCa, upregulated three types. Its significantly stage four showed both positive negative correlations depending type. Genomic revealed significant associations TMB 13 MSI 11 Pathway enrichment (Hallmark-GSEA KEGG-GSEA) indicated strong responses, progression. Immune infiltration predominantly association except low-grade gliomas (LGG). CIBERSORT demonstrated correlated positively resting memory CD4 cells, eosinophils, monocytes, mast B negatively M1 macrophages, follicular helper M0 also immune-regulatory molecules. reduced lines compared their normal counterparts. Kaplan-Meier survival higher better overall patients inhibited progression promoted tumor-killing ability microenvironment (TME). tumor-suppressive properties, downregulation most cancers, favorable prognosis enhanced responses. functions as suppressor improved outcomes. These findings suggest potential biomarker for diagnosis prognosis.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: April 1, 2025
The prognosis for head and neck squamous cell carcinoma (HNSCC) remains unfavorable, primarily due to significant therapeutic resistance the absence effective interventions. A major obstacle in cancer treatment is persistent of cells a variety modalities. tumor microenvironment (TME) which includes encompasses all non-malignant components their metabolites within tissue, plays crucial role this context. distinct characteristics HNSCC TME facilitate growth, invasion, metastasis, treatment. This review provides comprehensive overview components, with particular focus on tumor-associated macrophages (TAMs), regulatory T (Tregs), myeloid-derived suppressor (MDSCs), cancer-associated fibroblasts (CAFs), extracellular matrix, reprogrammed metabolic processes, products. It elucidates contributions modulating chemotherapy, radiotherapy, targeted therapy, immunotherapy HNSCC, explores novel strategies targeting management.
Language: Английский
Citations
0