1. Cell of origin in biliary tract cancers and clinical implications
- Author
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Philipp K. Haber, Agrin Moeini, and Daniela Sia
- Subjects
ER, estrogen receptor ,ARID1A ,Cell of origin ,ERBB2/3, Erb-B2 Receptor Tyrosine Kinase 2/3 ,TP53, Tumor Protein P53 ,PRKACA/B, Protein Kinase CAMP-Activated Catalytic Subunit Alpha/Beta ,Review ,Personalized therapy ,NA, not applicable ,RNF43, Ring Finger Protein 43 ,Lineage tracing ,PIK3CA, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha ,Bioinformatics ,medicine.disease_cause ,Cholangiocarcinoma ,ORR, objective response rate ,Immunology and Allergy ,iCCA, intrahepatic cholangiocarcinoma ,BAP1 ,CDKN2A/B, cyclin-dependent kinase inhibitor 2A/B ,Gastroenterology ,TBG, thyroid binding globulin ,Genomics ,PBG, peribiliary gland ,pCCA, perihilar cholangiocarcinoma ,BTC, biliary tract cancer ,GBC, gallbladder cancer ,Biliary tract ,CLC, cholangiolocarcinoma ,eCCA, extrahepatic cholangiocarcinoma ,KRAS ,FGFR2, Fibroblast Growth Factor Receptor 2 ,CK, cytokeratin ,DCR, disease control rate ,NAFLD, non-alcoholic fatty liver disease ,CCA, cholangiocarcinoma ,FGFR, fibroblast growth factor receptor ,MST1, Macrophage Stimulating 1 ,NASH, non-alcoholic steatohepatitis ,PLC, primary liver cancer ,Biliary tract cancers ,IDH, isocitrate dehydrogenase ,NTRK, Neurotrophic Receptor Tyrosine Kinase 1 ,Biology ,GEMM, genetically engineered mouse models ,WHO, World Health Organization ,OS, overall survival ,PFS, progression- free survival ,Prominin-1 ,HPCs, hepatic progenitor cells ,Internal Medicine ,medicine ,Gallbladder cancer ,CoH, Canal of Hering ,ARID1A, AT-rich interactive domain-containing protein 1A ,Hepatology ,BAP1, BRCA1-associated protein 1 ,PROM1, Prominin 1 ,mo, months ,medicine.disease ,KRAS, Kirsten Rat Sarcoma Viral Oncogene Homolog ,NR, not reported ,NGS, next-generation sequencing ,MET, Hepatocyte Growth Factor Receptor ,PSC, primary sclerosing cholangitis ,SMAD4, SMAD Family Member 4 ,HCC, hepatocellular carcinoma ,BRAF, v-Raf murine sarcoma viral oncogene homolog B ,dCCA, distal cholangiocarcinoma - Abstract
Summary Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level. Such complex heterogeneity poses a substantial obstacle to effective interventions. It is widely accepted that the observed heterogeneity may be the result of a complex interplay of different elements, including risk factors, distinct molecular alterations and multiple potential cells of origin. The use of genetic lineage tracing systems in experimental models has identified cholangiocytes, hepatocytes and/or progenitor-like cells as the cells of origin of BTCs. Genomic evidence in support of the distinct cell of origin hypotheses is growing. In this review, we focus on recent advances in the histopathological subtyping of BTCs, discuss current genomic evidence and outline lineage tracing studies that have contributed to the current knowledge surrounding the cell of origin of these tumours.
- Published
- 2021