Therapy of Primary Liver Cancer DOI Creative Commons
Mei Feng, Yisheng Pan, Ruirui Kong

et al.

The Innovation, Journal Year: 2020, Volume and Issue: 1(2), P. 100032 - 100032

Published: Aug. 1, 2020

•Primary liver cancer comprises HCC, ICC, cHCC-ICC, which are markedly distinct in their epidemiology, clinical features and response to therapy•HCC is viral infection-related malignancy with specific histological features, whereas ICC associated chronic inflammation•HCC prone respond targeted therapy, immunotherapy, antiviral agents, ICCs benefit from chemotherapy, immunotherapy•Combined cHCC-ICC subclass shows strong ICC-like considered be treated like mixed resembles HCC Primary (PLC) a fatal disease that affects millions of lives worldwide. PLC the leading cause cancer-related deaths incidence rate predicted rise coming decades. can categorized into three major subtypes: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), combined HCC-ICC. These subtypes respect clinicopathological genetic alterations, managements, thoroughly summarized this review. The state treatment strategies for each subtype, including currently approved drugs potential novel therapies, also discussed.

Language: Английский

Cholangiocarcinoma 2020: the next horizon in mechanisms and management DOI Creative Commons
Jesús M. Bañales, José J.G. Marı́n, Ángela Lamarca

et al.

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

Citations

1749
Tumour evolution in hepatocellular carcinoma DOI
Amanda J. Craig, Johann von Felden, Teresa García‐Lezana

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2019, Volume and Issue: 17(3), P. 139 - 152

Published: Dec. 2, 2019

Language: Английский

Citations

688
Liver tumour immune microenvironment subtypes and neutrophil heterogeneity DOI
Ruidong Xue, Qiming Zhang, Qi Cao

et al.

Nature, Journal Year: 2022, Volume and Issue: 612(7938), P. 141 - 147

Published: Nov. 9, 2022

Language: Английский

Citations

481
Advances in molecular classification and precision oncology in hepatocellular carcinoma DOI Creative Commons
Sandra Rebouissou, Jean–Charles Nault

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 72(2), P. 215 - 229

Published: Jan. 15, 2020

Language: Английский

Citations

438
Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma DOI Creative Commons
Min Zhang,

Hui Yang,

Lingfei Wan

et al.

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 73(5), P. 1118 - 1130

Published: June 5, 2020

Intrahepatic cholangiocarcinoma (ICC) is the second most common liver malignancy. ICC typically features remarkable cellular heterogeneity and a dense stromal reaction. Therefore, comprehensive understanding of diversity interplay between malignant cells niche essential to elucidate mechanisms driving progression develop therapeutic approaches.Herein, we performed single-cell RNA sequencing (scRNA-seq) analysis on unselected viable from 8 human ICCs adjacent samples transcriptomic landscape intercellular communication network. Additionally, applied negative selection strategy enrich fibroblast populations in 2 other investigate diversity. The results analyses were validated using multiplex immunofluorescence staining, bulk datasets, functional vitro vivo experiments.We sequenced total 56,871 single derived tissues identified diverse tumor, immune, cells. Malignant displayed high degree inter-tumor heterogeneity. Moreover, tumor-infiltrating CD4 regulatory T exhibited highly immunosuppressive characteristics. We 6 distinct subsets, which majority CD146-positive vascular cancer-associated fibroblasts (vCAFs), with expressed microvasculature signatures levels interleukin (IL)-6. Functional assays indicated that IL-6 secreted by vCAFs induced significant epigenetic alterations cells, particularly upregulating enhancer zeste homolog (EZH2) thereby enhancing Furthermore, cell-derived exosomal miR-9-5p elicited expression promote tumor progression.Our dataset delineates ICCs, underlining importance crosstalk vCAFs, revealing potential targets.Intrahepatic an aggressive chemoresistant Better complex transcriptional architecture these tumors will help development more effective therapies. Herein, have important interactions cancer stroma, could implications.

Language: Английский

Citations

424
The immunological and metabolic landscape in primary and metastatic liver cancer DOI
Xin Li, Pierluigi Ramadori, Dominik Pfister

et al.

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

Published: July 29, 2021

Language: Английский

Citations

406
Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma DOI Creative Commons
Daniel Wai‐Hung Ho, Yu‐Man Tsui, Lo‐Kong Chan

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 17, 2021

Abstract Interaction between tumor cells and immune in the microenvironment is important cancer development. Immune interact with to shape this process. Here, we use single-cell RNA sequencing analysis delineate landscape heterogeneity a cohort of patients HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress T cell infiltration TIGIT-NECTIN2 interaction regulates immunosuppressive environment. The state transition towards more exhaustive status exemplifies overall cancer-promoting immunocellular landscape. Furthermore, global molecular profiles reveals co-existence intra-tumoral inter-tumoral heterogeneity, but apparent latter. This intercellular interactions provides mechanistic information for design efficacious immune-oncology treatments carcinoma.

Language: Английский

Citations

221
Long noncoding RNA LINC00662 promotes M2 macrophage polarization and hepatocellular carcinoma progression via activating Wnt/β‐catenin signaling DOI Creative Commons
Xiaohui Tian, Yuanyuan Wu, Yating Yang

et al.

Molecular Oncology, Journal Year: 2019, Volume and Issue: 14(2), P. 462 - 483

Published: Dec. 2, 2019

Tumor‐associated macrophages have important roles in hepatocellular carcinoma (HCC) initiation and progression. Long noncoding RNAs (lncRNAs) also been reported to be involved HCC. In this study, we explored how lncRNA LINC00662 may influence HCC progression through both tumor cell‐dependent macrophage‐dependent mechanisms. was found upregulated HCC, high levels correlated with poor survival of patients. WNT3A expression secretion via competitively binding miR‐15a, miR‐16, miR‐107. Through inducing secretion, activated Wnt/β‐catenin signaling cells an autocrine manner further promoted cell proliferation, cycle, invasion, while repressing apoptosis. addition, acting a paracrine M2 macrophage polarization. Via activating polarization, significantly growth metastasis vivo . Hence, targeting provide novel therapeutic strategy against

Language: Английский

Citations

177
Combined hepatocellular-cholangiocarcinoma: An update DOI Creative Commons
Aurélie Beaufrère, Julien Caldéraro, Valérie Paradis

et al.

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 74(5), P. 1212 - 1224

Published: Feb. 5, 2021

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumour that exhibits both hepatocytic and biliary differentiation. Classical risk factors for hepatocellular carcinoma (HCC) seem to also predispose patients the development of cHCC-CCA. The pathological definition cHCC-CCA has significantly evolved over time. last 2019 WHO classification highlighted diagnosis should be primarily based on morphology using routine stainings, with additional immunostaining used refine identification subtypes. Among them, "intermediate cell carcinoma" recognised as specific subtype, while "cholangiolocellular now considered subtype iCCA. Increasing molecular evidence supports clonal nature parallels its biphenotypic histological appearance, genetic alterations are classically observed in HCC and/or That said, morphological still challenging radiologists pathologists, especially biopsy specimens. Identification cHCC-CCA's origin remains an area active research. Its prognosis generally worse than HCC, similar Resection lymph node dissection unfortunately only curative option Thus, there urgent need develop therapeutic strategies this unique clinical entity.

Language: Английский

Citations

152
The Hippo Pathway in Liver Homeostasis and Pathophysiology DOI
Jordan H. Driskill, Duojia Pan

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2020, Volume and Issue: 16(1), P. 299 - 322

Published: Nov. 25, 2020

Studies of the regenerative capacity liver have converged on Hippo pathway, a serine/threonine kinase cascade discovered in Drosophila and conserved from unicellular organisms to mammals. Genetic studies mouse rat livers revealed that pathway is key regulator size, regeneration, development, metabolism, homeostasis perturbations can lead development common diseases, such as fatty disease cancer. In turn, pharmacological targeting may be utilized boost regeneration prevent progression diseases. We review current insights provided by into pathophysiology. Furthermore, we present path forward for future understand how newly identified components control physiology regulated liver.

Language: Английский

Citations

150