Targeting cancer metabolism in the era of precision oncology

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 21(2), P. 141 - 162

Published: Dec. 3, 2021

Language: Английский

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Glutamine reliance in cell metabolism

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(9), P. 1496 - 1516

Published: Sept. 1, 2020

Abstract As knowledge of cell metabolism has advanced, glutamine been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence drug resistance, glutaminolysis-induced reprogramming presenting strategies target in cancer cells. In this review, we introduce various biosynthetic bioenergetic roles based compartmentalization explain why cells exhibit reliance glutamine. Additionally, examined whether derivatives contribute epigenetic regulation associated with tumorigenesis. addition, discussing transporters, propose for therapeutic intervention cancer.

Language: Английский

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Genetic and biological hallmarks of colorectal cancer

Genes & Development, Journal Year: 2021, Volume and Issue: 35(11-12), P. 787 - 820

Published: June 1, 2021

Colorectal cancer has served as a genetic and biological paradigm for the evolution of solid tumors, these insights have illuminated early detection, risk stratification, prevention, treatment principles. Employing hallmarks framework, we provide conceptual framework to understand how alterations in colorectal drive cell biology properties shape heterotypic interactions across cells tumor microenvironment. This review details research advances pertaining genetics cancer, emerging concepts gleaned from immune single-cell profiling, critical remaining knowledge gaps influencing development effective therapies this that remains major public health burden.

Language: Английский

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Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

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Mitochondrial DNA copy number in human disease: the more the better?

FEBS Letters, Journal Year: 2020, Volume and Issue: 595(8), P. 976 - 1002

Published: Dec. 12, 2020

Most of the genetic information has been lost or transferred to nucleus during evolution mitochondria. Nevertheless, mitochondria have retained their own genome that is essential for oxidative phosphorylation (OXPHOS). In mammals, a gene‐dense circular mitochondrial DNA (mtDNA) about 16.5 kb encodes 13 proteins, which constitute only 1% proteome. Mammalian mtDNA present in thousands copies per cell and mutations often affect fraction them. pathogenic human are recessive cause OXPHOS defects if above certain critical threshold. However, emerging evidence strongly suggests proportion mutated not determinant disease but also absolute copy number matters. this review, we critically discuss current knowledge role regulation various types diseases, including disorders, neurodegenerative disorders cancer, ageing. We provide an overview new exciting therapeutic strategies directly manipulate restore diseases.

Language: Английский

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The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure

Cell Metabolism, Journal Year: 2020, Volume and Issue: 33(3), P. 629 - 648.e10

Published: Dec. 17, 2020

Language: Английский

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Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Nov. 1, 2022

Colorectal cancer (CRC) is the third most common and second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark cancer, Warburg effect promotes metastasis remodels tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation drug resistance. Targeting metabolism would be promising method for treatment CRC. In this review, we summarize information about roles in microenvironment to elucidate mechanisms governing identify novel targets therapy.

Language: Английский

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High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity

Cell Reports, Journal Year: 2021, Volume and Issue: 35(10), P. 109212 - 109212

Published: June 1, 2021

Obesity is an established risk factor for cancer in many tissues. In the mammalian intestine, a pro-obesity high-fat diet (HFD) promotes regeneration and tumorigenesis by enhancing intestinal stem cell (ISC) numbers, proliferation, function. Although PPAR (peroxisome proliferator-activated receptor) nuclear receptor activity has been proposed to facilitate these effects, their exact role unclear. Here we find that, loss-of-function vivo models, PPARα PPARδ contribute HFD response ISCs. Mechanistically, both PPARs do so robustly inducing downstream fatty acid oxidation (FAO) metabolic program. Pharmacologic genetic disruption of CPT1A (the rate-controlling enzyme mitochondrial FAO) blunts phenotype Furthermore, inhibition dampens pro-tumorigenic consequences on early tumor incidence progression. These findings demonstrate that HFD-activated FAO program creates therapeutic opportunity counter effects ISCs tumorigenesis.

Language: Английский

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Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10037 - 10037

Published: Sept. 2, 2022

Aerobic glycolysis is an emerging hallmark of many human cancers, as cancer cells are defined a “metabolically abnormal system”. Carbohydrates metabolically reprogrammed by its metabolizing and catabolizing enzymes in such cells. Normal acquire their energy from oxidative phosphorylation, while glycolysis, known the “Warburg effect”. Energy–metabolic differences easily found growth, invasion, immune escape anti-tumor drug resistance The pathway carried out multiple enzymatic steps yields two pyruvate molecules one glucose (Glc) molecule orchestral reaction enzymes. Uncontrolled or abnormally activated observed metabolism with enhanced levels glycolytic proteins activities. In effect”, tumor utilize supplied lactic acid-based fermentative operated glycolysis-specific hexokinase (HK), keto-HK-A, Glc-6-phosphate isomerase, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, phosphofructokinase (PFK), phosphor-Glc isomerase (PGI), fructose-bisphosphate aldolase, phosphoglycerate (PG) kinase (PGK)1, triose phosphate PG mutase (PGAM), glyceraldehyde-3-phosphate dehydrogenase, enolase, isozyme type M2 (PKM2), dehydrogenase (PDH), PDH lactate dehydrogenase. They related to flux. key involved directly linked oncogenesis resistance. Among metabolic enzymes, PKM2, PGK1, HK, keto-HK-A nucleoside diphosphate also have protein Because glycolysis-generated not enough, cell-favored produce low ATP level seems be non-efficient for growth self-protection. Thus, Warburg effect still attractive phenomenon understand favored cancer. If basic properties effect, including genetic mutations signaling shifts considered, anti-cancer therapeutic targets can raised. Specific therapeutics targeting aerobic hypoxic microenvironments been developed kill present review deals tumor-specific revisited viewpoint recent progress.

Language: Английский

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Metabolism and Colorectal Cancer

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 18(1), P. 467 - 492

Published: Nov. 2, 2022

Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal cellular waste in nutrient-poor environments. Intestinal stem (ISCs), primary cell origin for CRCs, must adapt their along adenoma-carcinoma sequence to unique features complex microenvironment that include interactions with intestinal epithelial cells, immune stromal commensal microbes, dietary components. Emerging evidence implicates modifiable risk factors related environment, such as diet, important pathogenesis. Here, we focus on describing ISCs, diets influence initiation, genetics metabolism, tumor microenvironment. The mechanistic links between environmental factors, metabolic adaptations, enhancing or supporting tumorigenesis becoming better understood. Thus, greater knowledge holds promise improved prevention treatment.

Language: Английский

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