YAP/TAZ as master regulators in cancer: modulation, function and therapeutic approaches

Nature Cancer, Год журнала: 2022, Номер unknown

Опубликована: Дек. 23, 2022

Язык: Английский

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Acetyl-CoA metabolism in cancer

Nature reviews. Cancer, Год журнала: 2023, Номер 23(3), С. 156 - 172

Опубликована: Янв. 19, 2023

Few metabolites can claim a more central and versatile role in cell metabolism than acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is produced during nutrient catabolism to fuel the tricarboxylic acid cycle essential building block for fatty isoprenoid biosynthesis. It also functions as signalling metabolite substrate lysine acetylation reactions, enabling modulation of protein response acetyl-CoA availability. Recent years have seen exciting advances our understanding normal physiology cancer, buoyed by new mouse models, vivo stable-isotope tracing approaches improved methods measuring acetyl-CoA, including specific subcellular compartments. Efforts target metabolic enzymes are advancing, with one therapeutic agent targeting synthesis receiving approval from US Food Drug Administration. In this Review, we give an overview regulation cancer relevance major pathways which participates. We further discuss recent tissues tumours potential these therapeutically. conclude commentary on emerging nodes that may impact biology.

Язык: Английский

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Drug repurposing for cancer therapy

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

Опубликована: Апрель 18, 2024

Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.

Язык: Английский

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Exhaustion-associated cholesterol deficiency dampens the cytotoxic arm of antitumor immunity

Cancer Cell, Год журнала: 2023, Номер 41(7), С. 1276 - 1293.e11

Опубликована: Май 26, 2023

Язык: Английский

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The contribution of fungi to the global economy

Fungal Diversity, Год журнала: 2023, Номер 121(1), С. 95 - 137

Опубликована: Июль 1, 2023

Abstract Fungi provide ecological and environmental services to humans, as well health nutritional benefits, are vital numerous industries. Fermented food beverage products from fungi circulating in the market, generating billions of USD. However, highest potential monetary value is their role blue carbon trading because ability sequester large amounts soil. There no conclusive estimates available on global fungi, primarily there limited data for extrapolation. This study outlines contribution economy provides a first attempt at quantifying fungi. Our estimate USD 54.57 trillion starting point that can be analysed improved, highlighting significance providing an appreciation value. paper identifies different economically valuable provided by By giving all important fungal products, services, industrial applications underscores biodiversity conservation. Furthermore, if established, they will considered future policies effective ecosystem management.

Язык: Английский

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Statin shapes inflamed tumor microenvironment and enhances immune checkpoint blockade in non–small cell lung cancer

JCI Insight, Год журнала: 2022, Номер 7(18)

Опубликована: Авг. 9, 2022

Immune checkpoint blockade (ICB) therapy has achieved breakthroughs in the treatment of advanced non–small cell lung cancer (NSCLC). Nevertheless, low response due to immuno-cold (i.e., tumors with limited tumor-infiltrating lymphocytes) tumor microenvironment (TME) largely limits application ICB therapy. Based on glycolytic/cholesterol synthesis axis, a stratification framework for EGFR-WT NSCLC was developed summarize metabolic features and immuno-hot tumors. The cholesterol subgroup displays worst prognosis NSCLC, significant enrichment gene signature, indicating that targeting is essential NSCLC. Statin, inhibitor synthesis, can suppress aggressiveness vitro vivo also drastically reverse phenotype an inflamed vivo. This change led higher Moreover, both our in-house data meta-analysis further support statin significantly enhance efficacy. In terms preliminary mechanisms, could transcriptionally inhibit PD-L1 expression induce ferroptosis cells. Overall, we reveal significance demonstrate improved therapeutic efficacy combination statin. These findings provide clinical insight treat patients

Язык: Английский

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Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer

Pharmaceuticals, Год журнала: 2022, Номер 15(2), С. 151 - 151

Опубликована: Янв. 26, 2022

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered first-line therapy for hypercholesterolemia, both primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, platelet aggregation-inhibiting effects. preventive effect on atherothrombotic stroke has well established, but can influence other cerebrovascular diseases. This suggests that many neuroprotective effects in addition lowering cholesterol. Furthermore, research cause pro-apoptotic, growth-inhibitory, pro-differentiation various malignancies. Preclinical clinical evidence tumor growth induce apoptosis specific cancer cell types. pleiotropic diseases established; however, patients not fully elucidated still controversial. review discusses recent cancer. Additionally, this study describes pharmacological action focusing aspect 'beyond lipid-lowering'.

Язык: Английский

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Repurposing drugs to treat cardiovascular disease in the era of precision medicine

Nature Reviews Cardiology, Год журнала: 2022, Номер 19(11), С. 751 - 764

Опубликована: Май 23, 2022

Язык: Английский

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Protein lipidation in health and disease: molecular basis, physiological function and pathological implication

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

Опубликована: Март 15, 2024

Abstract Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli internal changes. Among these, protein lipidations which refer lipid attachment are prominent, primarily encompassing five types including S-palmitoylation, N-myristoylation, S-prenylation, glycosylphosphatidylinositol (GPI) anchor cholesterylation. Lipid plays an essential role regulation trafficking, localisation, stability, conformation, interactions signal transduction by enhancing hydrophobicity. Accumulating evidence from genetic, structural, biomedical studies has consistently shown that lipidation is pivotal broad physiological functions inextricably linked a variety diseases. Decades dedicated research have driven development wide range drugs targeting lipidation, several agents been developed tested preclinical clinical studies, some which, such as asciminib lonafarnib FDA-approved for therapeutic use, indicating represents promising strategy. Here, we comprehensively review known regulatory enzymes catalytic mechanisms various types, outline impact on physiology disease, highlight potential targets progress, aiming provide comprehensive reference future research.

Язык: Английский

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Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers

Nature Medicine, Год журнала: 2024, Номер 30(4), С. 990 - 1000

Опубликована: Апрель 1, 2024

Children with rare, relapsed or refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling drug sensitivity testing (DST) patient-derived tumor cells, has potential to identify options when standard-of-care is exhausted. goal this prospective observational study was generate FPM data for pediatric patients cancer. primary objective determine the feasibility returning FPM-based recommendations in real time board (FPMTB) within a clinically actionable timeframe (<4 weeks). secondary assess clinical outcomes from enrolled study. Twenty-five solid hematological were enrolled; 21 underwent DST 20 also completed profiling. Median turnaround times genomics 10 days 27 days, respectively. Treatment made 19 (76%), whom 14 received therapeutic interventions. Six subsequent FPM-guided treatments. Among these patients, five (83%) experienced greater than 1.3-fold improvement progression-free survival associated their therapy relative previous therapy, demonstrated significant increase response rate compared those eight non-guided patients. findings our proof-of-principle illustrate positively impact care adolescent warrant further validation large studies. ClinicalTrials.gov registration: NCT03860376 .

Язык: Английский

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