How Warburg-Associated Lactic Acidosis Rewires Cancer Cell Energy Metabolism to Resist Glucose Deprivation DOI Open Access

Zoé Daverio,

Aneta Balcerczyk, Gilles J. P. Rautureau

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(5), P. 1417 - 1417

Published: Feb. 23, 2023

Lactic acidosis, a hallmark of solid tumour microenvironment, originates from lactate hyperproduction and its co-secretion with protons by cancer cells displaying the Warburg effect. Long considered side effect metabolism, lactic acidosis is now known to play major role in physiology, aggressiveness treatment efficiency. Growing evidence shows that it promotes cell resistance glucose deprivation, common feature tumours. Here we review current understanding how extracellular acting as combination enzymatic inhibitors, signal, nutrient, switch metabolism an oxidative metabolic phenotype, which allows withstand makes promising anticancer target. We also discuss about acidosis’ could be integrated whole-tumour what perspectives opens up for future research.

Language: Английский

Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy DOI Open Access

Taranatee Khan,

M Nagarajan,

Irene Kang

et al.

Journal of Personalized Medicine, Journal Year: 2025, Volume and Issue: 15(2), P. 50 - 50

Published: Jan. 27, 2025

Drug resistance remains a significant barrier to effective cancer therapy. Cancer cells evade treatment by reprogramming their metabolism, switching from glycolysis oxidative phosphorylation (OXPHOS), and relying on alternative carbon sources such as glutamine. These adaptations not only enable tumor survival but also contribute immune evasion through mechanisms reactive oxygen species (ROS) generation the upregulation of checkpoint molecules like PD-L1. This review explores potential targeting metabolic weaknesses in drug-resistant cancers enhance therapeutic efficacy. Key pathways involved resistance, including glycolysis, glutamine kynurenine pathway, are discussed. The combination inhibitors with (ICIs), particularly anti-PD-1/PD-L1 therapies, represents promising approach overcoming both mechanisms. Clinical trials combining therapies have shown early promise, further research is needed optimize combinations identify biomarkers for patient selection. In conclusion, metabolism blockade offers novel drug providing pathway improved outcomes Future directions include personalized treatments based profiles expanding other types.

Language: Английский

Citations

1
Amyloid Targeting-Gold Nanoparticles-Assisted X-ray Therapy Rescues Islet β-Cells from Amyloid Fibrils and Restores Insulin Homeostasis DOI
Helen Forgham,

Stetson Van Matre,

Ka Hang Karen Chung

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: 19(5), P. 5460 - 5474

Published: Jan. 30, 2025

Type-2-diabetes is a metabolic disorder where misfolding and oligomerization of islet amyloid polypeptide (IAPP) around islet-β cells oligomerizes participates in the pathology. The oligomeric stage toxic but transitory leads to formation mature fibrils. pathological specifics fibrils are poorly understood. Here, we demonstrate that IAPP amyloids make gel-like transition, increasing viscosity local microenvironment encasing impeding their ability sense glucose release insulin. Using dual-targeted gold nanoparticles (AuNPs) capped with amyloid-fragments βCasein anti-IAPP antibodies, show X-ray irradiation AuNPs when bound results therapeutic remodelling amyloids, reduction solution, restoration glucose/insulin homeostasis. This study establishes can participate progressive pathology type-2-diabetes by suppressing insulin responsiveness at single islet-cell level. It also identifies model reversal using AuNPs-mediated therapy, this approach be rationally expanded other pathologies, such as Alzheimer's Parkinson's diseases.

Language: Английский

Citations

1
Effects of hypoxia on the heart of the juvenile four-finger threadfin (Eleutheronema tetradactylum) based on physiological indicators and transcriptome analysis DOI Creative Commons
Yi Lu, Eric Amenyogbe, Ye Yang

et al.

Frontiers in Marine Science, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 5, 2025

This study evaluated the effects of hypoxia on heart juvenile four-finger threadfin ( Eleutheronema tetradactylum ) through physiological and transcriptome analysis. Juveniles with an average weight 122.82 g length 24.60 cm were used. Hypoxia significantly increased serum myocardial enzyme activities, including creatine kinase (CK), kinase-MB isoenzyme, lactate dehydrogenase (LDH), α-hydroxybutyrate (HDBH). These indicators initially rose then declined, reflecting cardiac stress suggesting their potential as early biomarkers for real-time aquaculture monitoring. Histological analysis revealed structural damage in fibers under hypoxia, increasing severity over time. underscores need to minimize oxygen fluctuations prevent tissue degeneration. Transcriptome identified upregulated genes involved cell communication, immune responses, intracellular signaling, offering targets breeding hypoxia-tolerant species. Kyoto Encyclopedia Genes Genomes pathway enrichment highlighted key pathways such mitogen-activated protein (MAPK), hypoxia-inducible factor-1 (HIF-1), endocytosis, phagosome formation. The MAPK plays a critical role cellular survival, proliferation, apoptosis. Hypoxia-induced activation MAPKs like ERK, JNK, p38 regulates stress-responsive genes. HIF-1 signaling homeostasis, HIF-1α stabilizing hypoxia-responsive VEGFA, which promotes vascular remodeling enhances delivery. findings collectively offer practical applications enhancing management, monitoring biochemical markers, adopting breeding, adjusting environmental conditions mitigate stress, ensuring better productivity sustainability. research provides foundation further studies molecular mechanisms

Language: Английский

Citations

1
IGF2BP1/AIFM2 axis regulates ferroptosis and glycolysis to drive hepatocellular carcinoma progression DOI
Wei Peng, Jie Liang,

Xuanlv Qian

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111660 - 111660

Published: Feb. 1, 2025

Language: Английский

Citations

1
How Warburg-Associated Lactic Acidosis Rewires Cancer Cell Energy Metabolism to Resist Glucose Deprivation DOI Open Access

Zoé Daverio,

Aneta Balcerczyk, Gilles J. P. Rautureau

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(5), P. 1417 - 1417

Published: Feb. 23, 2023

Lactic acidosis, a hallmark of solid tumour microenvironment, originates from lactate hyperproduction and its co-secretion with protons by cancer cells displaying the Warburg effect. Long considered side effect metabolism, lactic acidosis is now known to play major role in physiology, aggressiveness treatment efficiency. Growing evidence shows that it promotes cell resistance glucose deprivation, common feature tumours. Here we review current understanding how extracellular acting as combination enzymatic inhibitors, signal, nutrient, switch metabolism an oxidative metabolic phenotype, which allows withstand makes promising anticancer target. We also discuss about acidosis’ could be integrated whole-tumour what perspectives opens up for future research.

Language: Английский

Citations

19