Targeting glutamine metabolism as a therapeutic strategy for cancer

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(4), P. 706 - 715

Published: April 3, 2023

Abstract Proliferating cancer cells rely largely on glutamine for survival and proliferation. Glutamine serves as a carbon source the synthesis of lipids metabolites via TCA cycle, well nitrogen amino acid nucleotide synthesis. To date, many studies have explored role metabolism in cancer, thereby providing scientific rationale targeting treatment. In this review, we summarize mechanism(s) involved at each step metabolism, from transporters to redox homeostasis, highlight areas that can be exploited clinical Furthermore, discuss mechanisms underlying cell resistance agents target strategies overcoming these mechanisms. Finally, effects blockade tumor microenvironment explore maximize utility blockers

Language: Английский

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Amino acid metabolism in tumor biology and therapy

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 13, 2024

Abstract Amino acid metabolism plays important roles in tumor biology and therapy. Accumulating evidence has shown that amino acids contribute to tumorigenesis immunity by acting as nutrients, signaling molecules, could also regulate gene transcription epigenetic modification. Therefore, targeting will provide new ideas for treatment become an therapeutic approach after surgery, radiotherapy, chemotherapy. In this review, we systematically summarize the recent progress of malignancy their interaction with signal pathways well effect on microenvironment Collectively, highlight potential application future expectation.

Language: Английский

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Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 11, 2024

Abstract Diet, serving as a vital source of nutrients, exerts profound influence on human health and disease progression. Recently, dietary interventions have emerged promising adjunctive treatment strategies not only for cancer but also neurodegenerative diseases, autoimmune cardiovascular metabolic disorders. These demonstrated substantial potential in modulating metabolism, trajectory, therapeutic responses. Metabolic reprogramming is hallmark malignant progression, deeper understanding this phenomenon tumors its effects immune regulation significant challenge that impedes eradication. Dietary intake, key environmental factor, can tumor metabolism. Emerging evidence indicates might affect the nutrient availability tumors, thereby increasing efficacy treatments. However, intricate interplay between pathogenesis other diseases complex. Despite encouraging results, mechanisms underlying diet-based remain largely unexplored, often resulting underutilization management. In review, we aim to illuminate various interventions, including calorie restriction, fasting-mimicking diet, ketogenic protein restriction high-salt high-fat high-fiber aforementioned diseases. We explore multifaceted impacts these encompassing their immunomodulatory effects, biological impacts, molecular mechanisms. This review offers valuable insights into application therapies

Language: Английский

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Efficient plasma metabolic fingerprinting as a novel tool for diagnosis and prognosis of gastric cancer: a large-scale, multicentre study

Gut, Journal Year: 2023, Volume and Issue: 72(11), P. 2051 - 2067

Published: July 17, 2023

Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead high-performance blood tests towards GC diagnosis prognosis. We attempted develop diagnostic prognostic models for based on plasma metabolic information.We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort 264 prospective cohort. Discovery verification phases were through machine learning Cox regression fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, developed model was validated both NPELDI-MS ultra-performance liquid chromatography-MS (UPLC-MS).We demonstrated high throughput, desirable reproducibility limited centre-specific effects PMFs NPELDI-MS. In cohort, we achieved performance with areas under curves (AUCs) 0.862-0.988 discovery (n=1157 5 centres) independent external dataset (n=787 another 2 centres), different PMFs, including neural network, ridge regression, lasso support vector random forest. Further, panel consisting 21 metabolites constructed identified AUCs 0.921-0.971 0.907-0.940 dataset, respectively. (n=264 centre), UPLC-MS applied detect validate panel, 0.855-0.918 0.856-0.916, Moreover, prognosis scoring system which can effectively predict survival patients.We GC, also contribute advanced analysis diseases, but not GC.

Language: Английский

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Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 22, 2024

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated almost all the undifferentiated NPC cases. Over past three decades, radiation therapy chemotherapy have formed cornerstone treatment. However, recent advancements in immunotherapy introduced a range promising approaches for managing NPC. In light these developments, it has become evident that deeper understanding tumor microenvironment (TME) crucial. TME serves dual function, acting as promoter tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression enabling immune evasion. Consequently, comprehensive comprehension its intricate involvement initiation, progression, metastasis imperative development effective anticancer drugs. Moreover, given complexity inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy circumvent drug resistance. This review aims provide an in-depth exploration within context EBV-induced NPC, particular emphasis on pivotal role regulating intercellular communication shaping responses. Additionally, offers concise summary resistance mechanisms potential strategies their reversal, specifically relation chemoradiation therapy, targeted immunotherapy. Furthermore, advances clinical trials pertaining are discussed.

Language: Английский

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The role of RNA methylation in tumor immunity and its potential in immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: March 8, 2024

Abstract Glutamine metabolism plays a pivotal role in cancer progression, immune cell function, and the modulation of tumor microenvironment. Dysregulated glutamine has been implicated development responses, supported by mounting evidence. Cancer cells heavily rely on as critical nutrient for survival proliferation, while require activation proliferation during reactions. This metabolic competition creates dynamic tug-of-war between cells. Targeting transporters downstream enzymes involved holds significant promise enhancing anti-tumor immunity. A comprehensive understanding intricate molecular mechanisms underlying this interplay is crucial developing innovative therapeutic approaches that improve immunity patient outcomes. In review, we provide overview recent advances unraveling explore potential applications basic science discoveries clinical setting. Further investigations into regulation are expected to yield valuable insights, paving way future interventions.

Language: Английский

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The role of glutamate and glutamine metabolism and related transporters in nerve cells

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(2)

Published: Feb. 1, 2024

Glutamate and glutamine are the most abundant amino acids in blood play a crucial role cell survival nervous system. Various transporters found mitochondrial membranes, such as solute carriers (SLCs) superfamily, responsible for maintaining balance of glutamate synaptic cleft within cells. This affects metabolism non-essential acids.

Language: Английский

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Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 24, 2025

Language: Английский

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Nanomedicines Targeting Metabolic Pathways in the Tumor Microenvironment: Future Perspectives and the Role of AI

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 201 - 201

Published: March 13, 2025

Background: Tumor cells engage in continuous self-replication by utilizing a large number of resources and capabilities, typically within an aberrant metabolic regulatory network to meet their own demands. This dysregulation leads the formation tumor microenvironment (TME) most solid tumors. Nanomedicines, due unique physicochemical properties, can achieve passive targeting certain tumors through enhanced permeability retention (EPR) effect, or active deliberate design optimization, resulting accumulation TME. The use nanomedicines target critical pathways holds significant promise. However, requires careful selection relevant drugs materials, taking into account multiple factors. traditional trial-and-error process is relatively inefficient. Artificial intelligence (AI) integrate big data evaluate delivery efficiency nanomedicines, thereby assisting nanodrugs. Methods: We have conducted detailed review key papers from databases, such as ScienceDirect, Scopus, Wiley, Web Science, PubMed, focusing on reprogramming, mechanisms action development metabolism, application AI empowering nanomedicines. integrated content present current status research metabolism potential future directions this field. Results: Nanomedicines possess excellent TME which be utilized disrupt cells, including glycolysis, lipid amino acid nucleotide metabolism. disruption selective killing disturbance Extensive has demonstrated that AI-driven methodologies revolutionized nanomedicine development, while concurrently enabling precise identification molecular regulators involved oncogenic reprogramming pathways, catalyzing transformative innovations targeted cancer therapeutics. Conclusions: great Additionally, will accelerate discovery metabolism-related targets, empower optimization help minimize toxicity, providing new paradigm for development.

Language: Английский

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