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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Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

The Lancet Oncology, Journal Year: 2020, Volume and Issue: 21(6), P. 796 - 807

Published: May 13, 2020

Language: Английский

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Cholangiocarcinoma: Epidemiology and risk factors

Liver International, Journal Year: 2019, Volume and Issue: 39(S1), P. 19 - 31

Published: March 9, 2019

Cholangiocarcinoma (CCA) is a heterogeneous disease arising from complex interaction between host-specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit geographical variation, with much higher in parts of the Eastern world compared to West. These differences are likely reflect factors as well determinants. Of note, over past few decades, appear change subtypes show distinct epidemiological trends. trends need be interpreted caution given issues diagnosis, recording coding CCA. Epidemiological evidences suggest that general population some less frequent but associated risk, while others more common lower risk. Moreover, shared by intrahepatic both extrahepatic forms, seem specific for one two forms. Currently pathological conditions have been clearly development, other emerging; however, their impact increasing single etiological has provided many studies, known when or co-occur same patient. despite advancements knowledge aetiology, Western countries about 50% cases still diagnosed without any identifiable factor. It therefore conceivable undefined etiologic responsible recent increase (especially iCCA) worldwide.

Language: Английский

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FGF/FGFR signaling in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Sept. 2, 2020

Growing evidences suggest that the fibroblast growth factor/FGF receptor (FGF/FGFR) signaling has crucial roles in a multitude of processes during embryonic development and adult homeostasis by regulating cellular lineage commitment, differentiation, proliferation, apoptosis various types cells. In this review, we provide comprehensive overview current understanding FGF its organ development, injury repair, pathophysiology spectrum diseases, which is consequence dysregulation, including cancers chronic kidney disease (CKD). context, agonists antagonists for FGF-FGFRs might have therapeutic benefits multiple systems.

Language: Английский

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Cholangiocarcinoma

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: Sept. 9, 2021

Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. Each anatomic subtype has distinct genetic aberrations, clinical presentations therapeutic approaches. In endemic regions, liver fluke infection associated with CCA, owing to oncogenic effect chronic biliary tract inflammation. other CCA inflammation choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. Administration anthelmintic drug praziquantel decreases risk from flukes, reinfection common future vaccination strategies may more effective. Some patients are eligible for potentially curative surgical options, such resection transplantation. Genetic studies provided new insights into pathogenesis two aberrations that drive non-fluke-associated intrahepatic fibroblast growth factor receptor 2 fusions isocitrate dehydrogenase gain-of-function mutations, therapeutically targeted. desmoplastic cancer targeting tumour immune microenvironment might promising approach. remains disease further scientific needed improve patient outcomes. system often This Primer reviews epidemiology, pathophysiological mechanisms, diagnosis management cholangiocarcinoma, highlights experience directions.

Language: Английский

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Wnt–β-catenin signalling in liver development, health and disease

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2018, Volume and Issue: 16(2), P. 121 - 136

Published: Nov. 19, 2018

Language: Английский

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Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: A systematic review and meta-analysis

Journal of Hepatology, Journal Year: 2019, Volume and Issue: 72(1), P. 95 - 103

Published: Sept. 16, 2019

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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Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Feb. 20, 2021

Abstract Despite great success in cancer immunotherapy, immune checkpoint-targeting drugs are not the most popular weapon armory of therapy. Accumulating evidence suggests that tumor microenvironment plays a critical role anti-cancer immunity, which may result checkpoint blockade therapy being ineffective, addition to other novel immunotherapies patients. In present review, we discuss deficiencies current immunotherapies. More importantly, highlight regulators surveillance, immunological evasion, and potential for their further translation into clinical practice. Based on general targetability therapy, believe promising immunotherapeutic targets. Targeting microenvironment, alone or combination with drugs, might benefit patients future.

Language: Английский

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Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

Seminars in Liver Disease, Journal Year: 2019, Volume and Issue: 39(01), P. 026 - 042

Published: Jan. 17, 2019

Abstract Hepatocellular carcinoma (HCC) is associated with chronic inflammation and fibrosis arising from different etiologies, including hepatitis B C alcoholic nonalcoholic fatty liver diseases. The inflammatory cytokines tumor necrosis factor-α interleukin-6 their downstream targets nuclear factor kappa (NF-κB), c-Jun N-terminal kinase (JNK), signal transducer activator of transcription 3 drive inflammation-associated HCC. Further, while adaptive immunity promotes immune surveillance to eradicate early HCC, cells, such as CD8+ T Th17 can also stimulate HCC development. Thus, the role hepatic system in development a highly complex topic. This review highlights cytokine signals, NF-κB, JNK, innate immunity, stellate cells discusses whether these pathways could be therapeutic targets. authors will discuss cholangiocarcinoma metastasis because biliary tumor-associated stroma are essential for primary tumor-derived mediators promote formation “premetastasis niche” liver.

Language: Английский

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