Summary Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common types of primary tumors in the liver. Although major advances have been made in understanding the ...cellular and molecular mechanisms underlying liver carcinogenesis, HCC and ICC are still deadly cancers worldwide waiting for innovative therapeutic options. Growing evidence from the literature highlight the critical role of the tumor cell microenvironment in the pathogenesis of cancer diseases. Thus, targeting the microenvironment, particularly the crosstalk between tumor cells and stromal cells, has emerged as a promising therapeutic strategy. This strategy would be particularly relevant for liver cancers which frequently develop in a setting of chronic inflammation and microenvironment remodeling associated with hepatic fibrosis and cirrhosis, such processes in which hepatic stellate cells (HSC) greatly contribute. This review brings a genomic point of view on the alterations of the cellular microenvironment in liver cancers, particularly the stromal tissue within tumor nodules, emphasizing the importance of the crosstalk between tumor cells and stromal cells, notably activated HSC, in tumor onset and progression. Furthermore, potential therapeutic modalities of targeting the stroma and HSC are discussed.
Cholangiocarcinoma (CCA) is a deadly cancer worldwide associated with limited therapeutic options. A recent study published in Clinical Science by Wang and colleagues Clin. Sci. (2019) 133(18), ...1935-1953 brought new perspectives to CCA management and therapy by focusing on circular RNAs (circRNAs). CircRNAs belong to an emerging class of functional non-coding RNAs (ncRNAs) regulating numerous biological processes. Notably, circRNAs have been associated with cancer onset and progression, although reports in CCA are very limited so far. In this work, the expression of circular RNA circ-0000284 (aka circHIPK3) was specifically elevated in CCA cell lines, human tumor tissues and plasma exosomes. Gain and loss of function approaches were performed to better understand the molecular mechanisms regulated by circ-0000284. Notably, the authors evaluated the role of circ-0000284 as a microRNA (miRNA) sponge. By prediction analysis and functional tests, a direct interaction was demonstrated with miR-637 that targets lymphocyte antigen-6 E (LY6E). Increased expression of circ-0000284 was associated with enhanced migration, invasion and proliferation of CCA cell lines. Interestingly, exosomal-mediated circ-0000284 was reported to exhibit pro-oncogenic effects on surrounding normal cells. Altogether, these data highlight circRNAs not only as new players in CCA pathogenesis but also as promising molecules for innovative non-invasive biomarkers, as circRNAs are enriched and stable in exosomes. Further investigations on extracellular vesicles should provide the necessary tools to improve CCA diagnosis, and move toward targeted-therapies.
Hepatocellular carcinoma (HCC) is the most frequent type of primary cancer in the liver. However, far more common than HCC are liver metastases. Indeed, the liver is one of the most frequent sites of ...implantation of metastatic tumor cells originating from skin, colon and breast primary cancers.
Molecular classification of cholangiocarcinoma Louis, Corentin; Papoutsoglou, Panagiotis; Coulouarn, Cédric
Current opinion in gastroenterology,
2020-March, 2020-03-00, 20200301, 2020-03, Letnik:
36, Številka:
2
Journal Article
Recenzirano
PURPOSE OF REVIEWCholangiocarcinoma (CCA) are heterogeneous tumors that arise from the malignant transformation of cholangiocytes along the biliary tree. CCA heterogeneity occurs at multiple levels ...and results in resistance to therapy and poor prognosis. Here, we review the molecular classification of CCA by focusing on the latest progresses based on genetic, epigenetic, transcriptomic and proteomic profiles. In addition, we introduce the emerging field of radiogenomics.
RECENT FINDINGSGenome-wide integrative omics approaches have been widely reported by using large cohorts of CCA patients. Morphomolecular correlations have been established, including enrichment of FGFR2 gene fusions and IDH1/2 mutations in iCCA. A specific IDH mutant iCCA subtype displays high mitochondrial and low chromatin modifier expression linked to ARID1A promoter hypermethylation. Examples of translation of these classifications for the management of CCA have also been reported, with prediction of drug efficacy based on genetic alterations.
SUMMARYAlthough there is currently no international consensus on CCA morphomolecular classification, the recent initiatives developed under the umbrella of The European Network for the Study of Cholangiocarcinoma (ENSCCA) should favor new collaborative research. Identifying distinct molecular subgroups and developing appropriate targeted therapies will improve the clinical outcome of patients with CCA.
Introduction: Cholangiocarcinoma (CCA) is a rare, deadly cancer that is characterized by an abundant desmoplastic stroma. Late diagnoses and limited available effective treatments are major problems ...with this malignancy. Targeting of the tumor microenvironment (TME) has emerged as a potential therapeutic strategy.
Areas covered: In this review, we describe the role of the various compartments of the TME in CCA and focus on the preclinical rationale for the development of innovative therapies. Relevant literature was identified by a PubMed search covering the last decade (2010-2020).
Expert opinion: Low efficacy of surgery and cytotoxic chemotherapy emphasizes the need for new therapeutic strategies and companion biomarkers. Single-cell RNA sequencing of the stroma is yielding a critical functional characterization of TME in CCA and is paving the way for immunotherapies and cancer-associated fibroblast and extracellular matrix-oriented treatments. We believe that the development of treatments targeting the components of the TME will produce the best results if in combination with cytotoxic chemotherapy. Biomarkers should be developed to define the patient population of interest for each combination strategy.
Liver cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are deadly cancers that have risen in frequency globally and have limited curative therapeutic options ...
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