Targeting glutamine metabolism as a therapeutic strategy for cancer

Experimental & Molecular Medicine, Год журнала: 2023, Номер 55(4), С. 706 - 715

Опубликована: Апрель 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

Язык: Английский

---

Amino acid metabolism in tumor biology and therapy

Cell Death and Disease, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 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.

Язык: Английский

---

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

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 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

Язык: Английский

---

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

Gut, Год журнала: 2023, Номер 72(11), С. 2051 - 2067

Опубликована: Июль 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.

Язык: Английский

---

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

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Янв. 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.

Язык: Английский

---

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

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июнь 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.

Язык: Английский

---

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

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Март 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.

Язык: Английский

---

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

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(2)

Опубликована: Фев. 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.

Язык: Английский

---

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Янв. 29, 2024

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence mortality, deprives countless patients of health even life. According to global cancer statistics, there were an estimated 19.3 million new cases nearly 10 deaths in 2020, the age-standardized mortality rates 201.0 100.7 per 100,000, respectively. Although remarkable advancements have been made therapeutic strategies recently, overall prognosis remains optimistic. Consequently, are still many severe challenges be faced difficult problems solved therapy today. Epigallocatechin gallate (EGCG), natural polyphenol extracted from tea leaves, received much attention for antitumor effects. Accumulating investigations confirmed EGCG can inhibit tumorigenesis progression by triggering apoptosis, suppressing proliferation, invasion, migration, altering tumor epigenetic modification, overcoming chemotherapy resistance. Nevertheless, regulatory roles biomolecular mechanisms immune microenvironment, metabolic immunotherapy remain obscure. In this article, we summarized most recent updates about effects on microenvironment (TME), reprogramming, anti-cancer immunotherapy. The results demonstrated promote response cytotoxic lymphocytes dendritic cells (DCs), attenuate immunosuppression myeloid-derived suppressor (MDSCs) T (Tregs), tumor-promoting functions tumor-associated macrophages (TAMs), neutrophils (TANs), various stromal including cancer-associated fibroblasts (CAFs), endothelial (ECs), stellate cells, mesenchymal stem/stromal (MSCs). Additionally, suppress multiple reprogramming pathways, glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, nucleotide synthesis. Finally, EGCG, as immunomodulator checkpoint blockade, enhance immunotherapeutic efficacy may promising candidate conclusion, plays versatile TME which provides novel insights combined

Язык: Английский

---

Immunotherapy resistance in solid tumors: mechanisms and potential solutions

Cancer Biology & Therapy, Год журнала: 2024, Номер 25(1)

Опубликована: Фев. 22, 2024

While the emergence of immunotherapies has fundamentally altered management solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range cellular activities - from modification traditional paradigms immunity via antigen presentation and immunoregulation metabolic modifications manipulation tumor microenvironment. Intervening on intricate processes may provide clinical benefit patients with tumors by overcoming immunotherapies, which is why it become an area tremendous research interest practice-changing implications. This review details major ways avoid both natural through primary (innate) secondary (acquired) resistance, considers available emerging therapeutic approaches immunotherapy resistance.

Язык: Английский

---