Cell-programmed nutrient partitioning in the tumour microenvironment

Nature, Journal Year: 2021, Volume and Issue: 593(7858), P. 282 - 288

Published: April 7, 2021

Language: Английский

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Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy

Molecular Cell, Journal Year: 2020, Volume and Issue: 78(6), P. 1019 - 1033

Published: June 1, 2020

Language: Английский

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Metabolomics and Isotope Tracing

Cell, Journal Year: 2018, Volume and Issue: 173(4), P. 822 - 837

Published: May 1, 2018

Language: Английский

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The metabolism of cancer cells during metastasis

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(3), P. 162 - 180

Published: Jan. 18, 2021

Language: Английский

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Lactate: the ugly duckling of energy metabolism

Nature Metabolism, Journal Year: 2020, Volume and Issue: 2(7), P. 566 - 571

Published: July 20, 2020

Language: Английский

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Lactate metabolism in human health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 1, 2022

Abstract The current understanding of lactate extends from its origins as a byproduct glycolysis to role in tumor metabolism, identified by studies on the Warburg effect. shuttle hypothesis suggests that plays an important bridging signaling molecule coordinates among different cells, organs and tissues. Lactylation is posttranslational modification initially reported Professor Yingming Zhao’s research group 2019. Subsequent confirmed lactylation vital component function involved proliferation, neural excitation, inflammation other biological processes. An indispensable substance for various physiological cellular functions, regulatory aspects energy metabolism signal transduction. Therefore, comprehensive review summary presented clarify disease provide reference direction future research. This offers systematic overview homeostasis roles pathological processes, well effects diseases, particularly cancer.

Language: Английский

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Revisiting the Warburg effect: historical dogma versus current understanding

The Journal of Physiology, Journal Year: 2020, Volume and Issue: 599(6), P. 1745 - 1757

Published: Dec. 22, 2020

Abstract Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary, permanent and universal consequence of dysfunctional or impaired mitochondria compensating for poor ATP yield per mole glucose. Instead, in most tumours the Warburg effect an essential part ‘selfish’ metabolic reprogramming, which results from interplay between (normoxic/hypoxic) hypoxia‐inducible factor‐1 (HIF‐1) overexpression, oncogene activation (cMyc, Ras), loss function tumour suppressors (mutant p53, mutant phosphatase tensin homologue (PTEN), microRNAs sirtuins with suppressor functions), activated (PI3K–Akt–mTORC1, Ras–Raf–MEK–ERK–cMyc, Jak–Stat3) deactivated (LKB1–AMPK) signalling pathways, components microenvironment, HIF‐1 cooperation epigenetic mechanisms. Molecular functional processes include: (a) considerable acceleration glycolytic fluxes; (b) adequate generation unit time maintain energy homeostasis electrochemical gradients; (c) backup diversion intermediates facilitating biosynthesis nucleotides, non‐essential amino acids, lipids hexosamines; (d) inhibition pyruvate entry into mitochondria; (e) excessive formation accumulation lactate, stimulates growth suppression anti‐tumour immunity – addition, lactate can serve as source normoxic cancer cells drives malignant progression resistances conventional therapies; (f) cytosolic being mainly exported through upregulated lactate–proton symporters (MCT4), working together other H + transporters, carbonic anhydrases (CAII, CAIX), hydrate CO 2 oxidative metabolism form bicarbonate; (g) these proton export mechanisms, concert vascular drainage, responsible extracellular acidification, driving resistance (h) maintenance cellular redox low reactive oxygen species (ROS) formation; (i) p53 PTEN, inhibit mitochondrial biogenesis functions, negatively impacting respiration rate. The switch early event oncogenesis primarily supports cell survival. All all, effect, i.e. presence principle functioning mitochondria, constitutes major driver machinery, therapies, patient outcome. However, evidenced during last two decades, minority primary defects play key role promoting due mutations some Krebs cycle enzymes ROS overproduction. image

Language: Английский

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Navigating metabolic pathways to enhance antitumour immunity and immunotherapy

Nature Reviews Clinical Oncology, Journal Year: 2019, Volume and Issue: 16(7), P. 425 - 441

Published: March 26, 2019

Language: Английский

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Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

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

Published: Feb. 17, 2023

Abstract Having a hypoxic microenvironment is common and salient feature of most solid tumors. Hypoxia has profound effect on the biological behavior malignant phenotype cancer cells, mediates effects chemotherapy, radiotherapy, immunotherapy through complex mechanisms, closely associated with poor prognosis in various patients. Accumulating studies have demonstrated that normalization tumor vasculature, nanoparticle carriers biocarriers can effectively increase oxygen concentration microenvironment, improve drug delivery efficacy radiotherapy. They also infiltration innate adaptive anti-tumor immune cells to enhance immunotherapy. Furthermore, drugs targeting key genes hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, hypoxia-inducible factors downstream targets, be used for visualization quantitative analysis antitumor activity. However, relationship between an area research requires further exploration. Here, we investigated potential development cancer, changes signaling pathways occur adapt environments, mechanisms hypoxia-induced tolerance, chemotherapeutic enhanced radiation as well insights applications therapy.

Language: Английский

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Metabolomics in cancer research and emerging applications in clinical oncology

CA A Cancer Journal for Clinicians, Journal Year: 2021, Volume and Issue: 71(4), P. 333 - 358

Published: May 13, 2021

Abstract Cancer has myriad effects on metabolism that include both rewiring of intracellular to enable cancer cells proliferate inappropriately and adapt the tumor microenvironment, changes in normal tissue metabolism. With recognition fluorodeoxyglucose‐positron emission tomography imaging is an important tool for management many cancers, other metabolites biological samples have been spotlight diagnosis, monitoring, therapy. Metabolomics global analysis small molecule like ‐omics technologies can provide critical information about state are otherwise not apparent. Here, authors review how therapies interact with at cellular systemic levels. An overview metabolomics provided a focus currently available they applied clinical translational research setting. The also discuss could be further leveraged future improve patients cancer.

Language: Английский

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