Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 17(9), P. 557 - 588

Published: June 30, 2020

Abstract Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point the tree. Their incidence is increasing globally, currently accounting for ~15% all primary liver cancers and ~3% gastrointestinal malignancies. The silent presentation these combined with their aggressive nature refractoriness to chemotherapy contribute alarming mortality, representing ~2% cancer-related deaths worldwide yearly. current diagnosis CCA by non-invasive approaches not accurate enough, histological confirmation necessary. Furthermore, high heterogeneity CCAs genomic, epigenetic molecular levels severely compromises efficacy available therapies. In past decade, efforts have been made understand complexity develop new diagnostic tools therapies might help improve patient outcomes. this expert Consensus Statement, which endorsed European Network Study Cholangiocarcinoma, we aim summarize critically discuss latest advances in CCA, mostly focusing on classification, cells origin, genetic abnormalities, alterations, biomarker discovery treatments. horizon next decade from 2020 onwards highlighted.

Language: Английский

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The immunological and metabolic landscape in primary and metastatic liver cancer

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(9), P. 541 - 557

Published: July 29, 2021

Language: Английский

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Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(2), P. 558 - 580

Published: Sept. 27, 2021

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies treat HCC, such as targeted tyrosine kinase inhibitors, immune based and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation progression driven by reprogramming metabolism, particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal new nomenclature non-alcoholic (NAFLD), indicates growing appreciation metabolism the pathogenesis disease, thereby suggesting targeting abnormal treatment. In this review, we introduce directions highlighting targets glucose, acid, amino acid glutamine which are suitable intervention. We also summarize discuss agents studies deregulated Furthermore, opportunities challenges discovery development therapy discussed.

Language: Английский

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Lipid alterations in chronic liver disease and liver cancer

JHEP Reports, Journal Year: 2022, Volume and Issue: 4(6), P. 100479 - 100479

Published: March 26, 2022

Lipids are a complex and diverse group of molecules with crucial roles in many physiological processes, as well the onset, progression, maintenance cancers. Fatty acids cholesterol building blocks lipids, orchestrating these metabolic processes. In liver, lipid alterations prevalent cause consequence chronic hepatitis B C virus infections, alcoholic hepatitis, non-alcoholic fatty liver disease steatohepatitis. Recent developments lipidomics have also revealed that dynamic changes triacylglycerols, phospholipids, sphingolipids, ceramides, acids, involved development progression primary cancer. Accordingly, transcriptional landscape metabolism suggests carcinogenic role increasing sterol synthesis. However, limited mechanistic insights into nature hepatic lipidome so far hindered effective therapies.

Language: Английский

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Arginine reprograms metabolism in liver cancer via RBM39

Cell, Journal Year: 2023, Volume and Issue: 186(23), P. 5068 - 5083.e23

Published: Oct. 6, 2023

Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels elevated murine patient hepatocellular carcinoma (HCC), despite reduced expression synthesis genes. Tumor cells accumulate high due to increased uptake arginine-to-polyamine conversion. Importantly, the promote tumor formation via further reprogramming, including changes glucose, amino acid, nucleotide, fatty acid metabolism. Mechanistically, binds RNA-binding motif protein 39 (RBM39) control RBM39-mediated upregulation asparagine leads enhanced uptake, creating positive feedback loop sustain oncogenic Thus, second messenger-like molecule reprograms growth.

Language: Английский

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Metabolic reprogramming in cholangiocarcinoma

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(3), P. 849 - 864

Published: May 18, 2022

Language: Английский

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Comparing DESI-MSI and MALDI-MSI Mediated Spatial Metabolomics and Their Applications in Cancer Studies

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: July 18, 2022

Metabolic heterogeneity of cancer contributes significantly to its poor treatment outcomes and prognosis. As a result, studies continue focus on identifying new biomarkers metabolic vulnerabilities, both which depend the understanding altered metabolism in cancer. In recent decades, rise mass spectrometry imaging (MSI) enables situ detection large numbers small molecules tissues. Therefore, researchers look using MSI-mediated spatial metabolomics further study metabolites patients. this review, we examined two most commonly used techniques, MALDI-MSI DESI-MSI, some highlights their applications studies. We also described AFADESI-MSI as variation from DESI-MSI compare it with major techniques. Specifically, discussed results four types heterogeneous malignancies, including breast cancer, esophageal glioblastoma lung Multiple have effectively classified tissue subtypes information. addition, distribution trends key such fatty acids, high-energy phosphate compounds, antioxidants were identified. while visualization finer details requires improvement MSI past suggested be promising direction complexity pathophysiology.

Language: Английский

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Metabolic reprogramming and its clinical implication for liver cancer

Hepatology, Journal Year: 2023, Volume and Issue: 78(5), P. 1602 - 1624

Published: Jan. 3, 2023

Cancer cells often encounter hypoxic and hypo-nutrient conditions, which force them to make adaptive changes meet their high demands for energy various biomaterials biomass synthesis. As a result, enhanced catabolism (breakdown of macromolecules production) anabolism (macromolecule synthesis from bio-precursors) are induced in cancer. This phenomenon is called “metabolic reprogramming,” cancer hallmark contributing development, metastasis, drug resistance. HCC cholangiocarcinoma (CCA) 2 different liver cancers with intertumoral heterogeneity terms etiologies, mutational landscapes, transcriptomes, histological representations. In agreement, metabolism or CCA remarkably heterogeneous, although the glycolytic pathways an increase generation lactate (the Warburg effect) have been frequently detected those tumors. For example, tumors activated β-catenin addicted fatty acid catabolism, whereas derived avoid using acids. this review, we describe common metabolic alterations as well features unique subsets. We discuss NAFLD well, because will likely become leading etiology coming years due obesity epidemic Western world. Furthermore, outline clinical implication highlight computation systems biology approaches, such genome-wide models, valuable tool allowing us identify therapeutic targets develop personalized treatments patients.

Language: Английский

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PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 23, 2023

Abstract Serine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, using integrative metabolomics transcriptomics analyses, we show a heterogeneity between metabolite transcript profiles. Specifically, the level of serine hepatocellular carcinoma (HCC) tissues increased, whereas expression phosphoglycerate dehydrogenase (PHGDH), first rate-limiting enzyme biosynthesis pathway, markedly downregulated. Interestingly, increased obtained by enhanced PHGDH catalytic activity due to protein arginine methyltransferase 1 (PRMT1)-mediated methylation at 236. PRMT1-mediated activation potentiates synthesis, ameliorates oxidative stress, promotes HCC vitro vivo. Furthermore, correlates with hyperactivation accumulation human tissues, predictive poor prognosis patients. Notably, blocking TAT-tagged nonmethylated peptide inhibits restrains an patient-derived xenograft (PDX) model subcutaneous cell-derived model. Overall, our findings reveal suggest as potential therapeutic vulnerability HCC.

Language: Английский

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Deep whole-genome analysis of 494 hepatocellular carcinomas

Nature, Journal Year: 2024, Volume and Issue: 627(8004), P. 586 - 593

Published: Feb. 14, 2024

Language: Английский

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