Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Cells, Journal Year: 2021, Volume and Issue: 10(5), P. 1056 - 1056

Published: April 29, 2021

Cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. These alterations include (1) a shift from oxidative phosphorylation aerobic glycolysis support the increased need for ATP, (2) glutaminolysis NADPH regeneration, (3) altered flux through pentose phosphate pathway tricarboxylic acid cycle macromolecule generation, (4) lipid uptake, lipogenesis, cholesterol synthesis, (5) upregulation of one-carbon metabolism production NADH/NADPH, nucleotides, glutathione, (6) amino metabolism, (7) metabolism-based regulation apoptosis, (8) utilization alternative substrates, such as lactate acetate. Altered in cancer is controlled by tumor-host cell interactions, key oncogenes, tumor suppressors, other regulatory molecules, including non-coding RNAs. Changes pathways are dynamic, exhibit plasticity, often dependent on type microenvironment, leading thought Warburg Effect "reverse Effect" plasticity. Understanding complex nature these multiple can development new therapies.

Language: Английский

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Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(6), P. 323 - 339

Published: March 9, 2022

Language: Английский

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Brown-fat-mediated tumour suppression by cold-altered global metabolism

Nature, Journal Year: 2022, Volume and Issue: 608(7922), P. 421 - 428

Published: Aug. 3, 2022

Glucose uptake is essential for cancer glycolysis and involved in non-shivering thermogenesis of adipose tissues1-6. Most cancers use to harness energy their infinite growth, invasion metastasis2,7,8. Activation thermogenic metabolism brown tissue (BAT) by cold drugs instigates blood glucose adipocytes4,5,9. However, the functional effects global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure tumour-bearing mice conditions markedly inhibits various types solid tumours, including clinically untreatable such as pancreatic cancers. Mechanistically, cold-induced substantially decreases impedes glycolysis-based cells. The removal feeding a high-glucose diet under restore genetic deletion Ucp1-the key mediator BAT-thermogenesis-ablates cold-triggered anticancer effect. In pilot human study, mild activates substantial amount both healthy humans patient mitigated tissue. These findings provide previously undescribed concept paradigm therapy uses simple effective approach. We anticipate through any other approach, devices either alone or combination therapeutics, will general approach treatment

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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Liquid–liquid phase separation in tumor biology

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

Published: July 8, 2022

Abstract Liquid–liquid phase separation (LLPS) is a novel principle for explaining the precise spatial and temporal regulation in living cells. LLPS compartmentalizes proteins nucleic acids into micron-scale, liquid-like, membraneless bodies with specific functions, which were recently termed biomolecular condensates. Biomolecular condensates are executors underlying intracellular spatiotemporal coordination of various biological activities, including chromatin organization, genomic stability, DNA damage response repair, transcription, signal transduction. Dysregulation these cellular processes key event initiation and/or evolution cancer, emerging evidence has linked formation to malignant transformations tumor biology. In this review, we comprehensively summarize detailed mechanisms condensate biophysical function review recent major advances toward elucidating multiple involved cancer cell pathology driven by aberrant LLPS. addition, discuss therapeutic perspectives research most developed drug candidates targeting modulation that can be used combat tumorigenesis.

Language: Английский

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Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 21, 2022

Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergistic therapy. Because our self-assembling NPs are encapsulated membranes derived from glioma cells, they readily penetrate blood-brain barrier target GBM through homotypic recognition. After reaching tumors, oxidase converts into pyruvic acid (PA) hydrogen peroxide (H2O2). The PA inhibits cell growth by blocking histones expression inducing cell-cycle arrest. In parallel, H2O2 reacts delivered bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate to release energy, which used co-delivered photosensitizer chlorin e6 generation cytotoxic singlet oxygen kill cells. Such synergism ensures strong effects against both cell-line patient-derived xenograft models.

Language: Английский

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Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(12), P. 4327 - 4347

Published: Nov. 4, 2022

Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies, on account of its good safety long-term memory ability. Discouragingly, low patient response rates potential immune-related side effects make it rather challenging to literally bring from bench bedside. However, become evident that, although immunosuppressive microenvironment (TME) plays a pivotal role in facilitating progression metastasis, also provides various targets for remodeling TME, which can consequently bolster effectiveness antitumor suppression. Additionally, particular characteristics turn, be exploited as avenues designing diverse precise targeting nanomedicines. In general, is urgent necessity deliver nanomedicines thus improving therapeutic outcomes clinical translation prospects immunotherapy. Herein, we will illustrate several formation mechanisms TME. More importantly, variety strategies concerning TME strengthening patients' immune systems, reviewed. Ultimately, discuss existing obstacles future perspectives development Hopefully, thriving bloom vibrancy further exploration comprehensive cancer treatment.

Language: Английский

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Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

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

Published: Oct. 25, 2022

Immunotherapy for cancer is a rapidly developing treatment that modifies the immune system and enhances antitumor response. B7-H3 (CD276), member of B7 family plays an immunoregulatory role in T cell response, has been highlighted as novel potential target immunotherapy. shown to play inhibitory activation proliferation, participate tumor evasion influence both response behavior through different signaling pathways. expression found be aberrantly upregulated many types, association between poor prognosis established. targeting approaches rapidly, ongoing clinical trials are exploring safety efficacy profiles these therapies cancer. In this review, we summarize emerging research on function underlying pathways B7-H3, roles advances B7-H3-targeted therapy. Considering microenvironment characteristics results from preclinical models practice, indicates promising future immunotherapy, which might eventually contribute improvement immunotherapy will benefit patients.

Language: Английский

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The Bioavailability of Drugs—The Current State of Knowledge

Molecules, Journal Year: 2023, Volume and Issue: 28(24), P. 8038 - 8038

Published: Dec. 11, 2023

Drug bioavailability is a crucial aspect of pharmacology, affecting the effectiveness drug therapy. Understanding how drugs are absorbed, distributed, metabolized, and eliminated in patients' bodies essential to ensure proper safe treatment. This publication aims highlight relevance research its importance In addition biochemical activity, also plays critical role achieving desired therapeutic effects. may seem obvious, but it worth noting that can only produce expected effect if level concentration be achieved at point patient's body. Given differences between patients, dosages, administration forms, understanding controlling has become priority pharmacology. discusses basic concepts factors it. We looked various methods assessing bioavailability, both laboratory clinic. Notably, introduction new technologies tools this field vital achieve advances research. cases with poorly described providing deeper complex challenges they pose medical researchers practitioners. Simultaneously, article focuses on perspectives trends shape future regarding which development modern pharmacology context, offers an essential, meaningful contribution toward highlighting bioavailability's reliable patient The text identifies areas require further exploration.

Language: Английский

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Drug-induced oxidative stress in cancer treatments: Angel or devil?

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102754 - 102754

Published: May 18, 2023

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one the most significant biological events cancer progression. Cancer cells generally represent a higher level, which suggests dual therapeutic strategy by regulating status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, exhibits great anti-cancer capability, attributing to accumulation within cells, whereas restore homeostasis has been claimed fail several clinical practices. Targeting vulnerability pro-oxidants capable generating excessive reactive oxygen species (ROS) surfaced an important strategy. However, multiple adverse effects caused indiscriminate attacks uncontrolled drug-induced OS on normal tissues and drug-tolerant capacity some certain greatly limit their further applications. Herein, we review representative oxidative drugs summarize side organs, emphasizing that seeking balance between damage value exploiting next-generation OS-based chemotherapeutics.

Language: Английский

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