Current challenges to underpinning the genetic basis for cholangiocarcinoma

References

• Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17:557–588.
   PubMed Web of Science ®Google Scholar
• Rizvi S, Khan SA, Hallemeier CL, et al. Cholangiocarcinoma-evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15(2):95–111.
   PubMed Web of Science ®Google Scholar
• Alvaro D, Hassan C, Cardinale V, et al. Italian Clinical Practice Guidelines on Cholangiocarcinoma – part I: classification, diagnosis and staging. Dig Liver Dis. 2020;52(11):1282–1293.
   PubMedGoogle Scholar
• Selvadurai S, Mann K, Mithra S, et al. Cholangiocarcinoma miscoding in hepatobiliary centres. Eur J Surg Oncol. 2020;(3 Pt B). DOI:10.1016/j.ejso.2020.09.039
   PubMed Web of Science ®Google Scholar
• DeOliveira ML, Cunningham SC, Cameron JL, et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg. 2007;245(5):755–762.
   PubMed Web of Science ®Google Scholar
• Brunt E, Aishima S, Clavien P, et al. cHCC-CCA: consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation. Hepatology. 2018;68(1):113–126.
   PubMed Web of Science ®Google Scholar
• Ishii T, Ito T, Sumiyoshi S, et al. Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma. World J Surg Oncol. 2020;18(1):319
   PubMed Web of Science ®Google Scholar
• Munoz-Garrido P, Rodrigues PM. The jigsaw of dual hepatocellular–intrahepatic cholangiocarcinoma tumours. Nat Rev Gastroenterol Hepatol. 2019;16(11):653–655.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Cai H, Xu M-H, et al. Do the existing staging systems for primary liver cancer apply to combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma? Hepatobiliary Pancreat Dis Int. 2020;362:1273–1281.
   Google Scholar
• Bertuccio P, Malvezzi M, Carioli G, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019;71(1):104–114
   PubMed Web of Science ®Google Scholar
• Sripa B, Pairojkul C. Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroenterol. 2008;24(3):349–356.
   PubMed Web of Science ®Google Scholar
• Woradet S, Songserm N, Promthet S, et al. Health-Related Quality of Life and Survival of Cholangiocarcinoma Patients in Northeastern Region of Thailand. Bruns H, editor. PLoS One. 2016;11(9):e0163448.
   PubMed Web of Science ®Google Scholar
• Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: epidemiology and risk factors. Liver Int. 2019;39(S1):19–31.
   PubMed Web of Science ®Google Scholar
• Clements O, Eliahoo J, Kim JU, et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a systematic review and meta-analysis. J Hepatol. 2019;72(1):95–103.
   PubMed Web of Science ®Google Scholar
• Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168–2179.
   PubMed Web of Science ®Google Scholar
• Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268–1289.
   PubMed Web of Science ®Google Scholar
• Plentz RR, Malek NP. Systemic Therapy of Cholangiocarcinoma. Visc Med. 2016;32(6):427–430.
   PubMed Web of Science ®Google Scholar
• Scott AJ, Shroff RT. Moving the Needle Forward with Locoregional Treatment in Unresectable Cholangiocarcinoma - The Jury Is Still Out. JAMA Oncol. 2020;6(1):29–31.
   PubMed Web of Science ®Google Scholar
• Weigt J, Malfertheiner P. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. Expert Rev Gastroenterol Hepatol. 2010;4(4):395–397.
   PubMed Web of Science ®Google Scholar
• Valle JW, Furuse J, Jitlal M, et al. Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials. Ann Oncol. 2014;25(2):391–398.
   PubMed Web of Science ®Google Scholar
• Shroff RT, Javle MM, Xiao L, et al. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: a Phase 2 Clinical Trial. JAMA Oncol. 2019;5(6):824–830.
   PubMed Web of Science ®Google Scholar
• Lamarca A, Palmer DH, Wasan HS, et al. ABC-06 | a randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced/metastatic biliary tract cancers (ABC) previously-tr. J Clin Oncol. 2019;37(15_suppl):4003.
   Web of Science ®Google Scholar
• Martinez FJ, Shroff RT. Biliary tract cancers: systemic therapy for advanced disease. Chinese Clin Oncol. 2020;9(1):9–13.
   PubMed Web of Science ®Google Scholar
• Lamarca A, Edeline J, McNamara MG, et al. Current standards and future perspectives in adjuvant treatment for biliary tract cancers. Cancer Treat Rev. 2020;84:101936.
   PubMed Web of Science ®Google Scholar
• Hollebecque A, Silverman I, Owens S, et al. Comprehensive genomic profiling and clinical outcomes in patients (pts) with fibroblast growth factor receptor rearrangement-positive (FGFR2+) cholangiocarcinoma (CCA) treated with pemigatinib in the fight-202 trial. Ann Oncol. 2019;30:v276.
   Web of Science ®Google Scholar
• Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671–684.
   PubMed Web of Science ®Google Scholar
• Banales JM, Cardinale V, Carpino G, et al. Expert consensus document: cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016;13:261–280.
   PubMed Web of Science ®Google Scholar
• Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma: a spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg. 1996;224(4):463–475.
   PubMed Web of Science ®Google Scholar
• Cardinale V. Multiple cells of origin in cholangiocarcinoma underlie biological, epidemiological and clinical heterogeneity. World J Gastrointest Oncol. 2012;4(5):94.
   PubMed Web of Science ®Google Scholar
• Yamasaki S. Intrahepatic cholangiocarcinoma: macroscopic type and stage classification. J Hepatobiliary Pancreat Surg. 2003;10(4):288–291.
   PubMedGoogle Scholar
• Krasinskas AM. Cholangiocarcinoma. Surg Pathol Clin. 2018;11(2):403–429.
   PubMedGoogle Scholar
• Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and Development of the Liver. Dev Cell. 2010;18(2):175–189.
   PubMed Web of Science ®Google Scholar
• Cigliano A, Wang J, Chen X, et al. Role of the Notch signaling in cholangiocarcinoma. Expert Opin Ther Targets. 2017;21(5):471–483.
   PubMed Web of Science ®Google Scholar
• Fan B, Chen X, Willenbring H, et al. Cholangiocarcinomas can originate from hepatocytes in mice. J Clin Invest. 2012;122(8):2911–2915
   PubMed Web of Science ®Google Scholar
• Sekiya S, Suzuki A. Brief report Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes. J Clin Invest. 2012;122(11):3914–3918.
   PubMed Web of Science ®Google Scholar
• Wang B, Zhao L, Fish M, et al. Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver. Nature. 2015;524(7564):180–185.
   PubMed Web of Science ®Google Scholar
• Font-Burgada J, Shalapour S, Ramaswamy S, et al. Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer. Cell. 2015;162(4):766–779.
   PubMed Web of Science ®Google Scholar
• Chung BK, Karlsen TH, Folseraas T. Cholangiocytes in the pathogenesis of primary sclerosing cholangitis and development of cholangiocarcinoma. Biochim Biophys Acta - Mol Basis Dis. 2018;1864(4):1390–1400.
   PubMed Web of Science ®Google Scholar
• Komuta M, Govaere O, Vandecaveye V, et al. Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. Hepatology. 2012;55(6):1876–1888.
   PubMed Web of Science ®Google Scholar
• Carpino G, Cardinale V, Folseraas T, et al. Neoplastic Transformation of the Peribiliary Stem Cell Niche in Cholangiocarcinoma Arisen in Primary Sclerosing Cholangitis. Hepatology. 2019;69(2):622–638.
   PubMed Web of Science ®Google Scholar
• Andersen JB, Spee B, Blechacz BR, et al. Genomic and Genetic Characterization of Cholangiocarcinoma Identifies Therapeutic Targets for Tyrosine Kinase Inhibitors. Gastroenterology. 2012;142:1021–1031.e15.
   PubMed Web of Science ®Google Scholar
• Lee SH, Simoneau EB, Karpinets T, et al. Genomic Profiling of Multifocal Intrahepatic Cholangiocarcinoma Reveals Intraindividual Concordance of Genetic Alterations. Carcinogenesis. 2020;29:2341–2386.
   Google Scholar
• Ong CK, Subimerb C, Pairojkul C, et al. Exome sequencing of liver fluke–associated cholangiocarcinoma. Nat Genet. 2012;44(6):690–693.
   PubMed Web of Science ®Google Scholar
• Wu Y, Su F, Kalyana-Sundaram S, et al. Identification of Targetable FGFR Gene Fusions in Diverse Cancers. Cancer Discov. 2013;3(6):636–647.
   PubMed Web of Science ®Google Scholar
• Zou S, Li J, Zhou H, et al. Mutational landscape of intrahepatic cholangiocarcinoma. Nat Commun. 2014;5(1):5696.
   PubMed Web of Science ®Google Scholar
• Borad MJ, Champion MD, Egan JB, et al. Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma. Horwitz MS, editor. PLoS Genet. 2014;10(2):e1004135.
   PubMed Web of Science ®Google Scholar
• Ross JS, Wang K, Gay L, et al. New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next‐Generation Sequencing. Oncologist. 2014;19(3):235–242.
   PubMed Web of Science ®Google Scholar
• Nakamura H, Arai Y, Totoki Y, et al. Genomic spectra of biliary tract cancer. Nat Genet. 2015;47(9):1003–1010.
   PubMed Web of Science ®Google Scholar
• Sia D, Losic B, Moeini A, et al. Massive parallel sequencing uncovers actionable FGFR2–PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma. Nat Commun. 2015;6(1):6087.
   PubMed Web of Science ®Google Scholar
• Boulter L, Guest RV, Kendall TJ, et al. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J Clin Invest. 2015;125(3):1269–1285.
   PubMed Web of Science ®Google Scholar
• Farshidfar F, Zheng S, Gingras M-C, et al. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles. Cell Rep. 2017;19(13):2878–2880.
   PubMed Web of Science ®Google Scholar
• Nepal C, O’Rourke CJ, Oliveira DVNP, et al. Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma. Hepatology. 2018;68(3):949–963.
   PubMed Web of Science ®Google Scholar
• O’Rourke CJ, Munoz-Garrido P, Aguayo EL, et al. Epigenome dysregulation in cholangiocarcinoma. Biochim Biophys Acta - Mol Basis Dis. 2018;1864(4):1423–1434.
   PubMed Web of Science ®Google Scholar
• O’Rourke CJ, Lafuente-Barquero J, Andersen JB. Epigenome Remodeling in Cholangiocarcinoma. Trends Cancer. 2019;5(6):335–350.
   PubMed Web of Science ®Google Scholar
• Wang P, Dong Q, Zhang C, et al. Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene. 2013;32(25):3091–3100.
   PubMed Web of Science ®Google Scholar
• Saha SK, Parachoniak CA, Ghanta KS, et al. Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer. Nature. 2014;513(7516):110–152.
   PubMed Web of Science ®Google Scholar
• Lee K, Song YS, Shin Y, et al. Intrahepatic cholangiocarcinomas with IDH1/2 mutation-associated hypermethylation at selective genes and their clinicopathological features. Sci Rep. 2020;10(1):1–10.
   PubMed Web of Science ®Google Scholar
• Yu Y, Liu Q, Li W, et al. Identification of a Novel EHBP1 ‐ MET Fusion in an Intrahepatic Cholangiocarcinoma Responding to Crizotinib. Oncologist. 2020;25(12):1005–1008
   PubMed Web of Science ®Google Scholar
• Jiao Y, Pawlik TM, Anders RA, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet. 2013;45(12):1470–1473.
   PubMed Web of Science ®Google Scholar
• Graham RP, Barr Fritcher EG, Pestova E, et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol. 2014;45(8):1630–1638.
   PubMed Web of Science ®Google Scholar
• Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: potential Targets for Intervention. Clin Cancer Res. 2018;24(17):4154–4161.
   PubMed Web of Science ®Google Scholar
• Javle M, Bekaii-Saab T, Jain A, et al. Biliary cancer: utility of next-generation sequencing for clinical management. Cancer. 2016;122(24):3838–3847.
   PubMed Web of Science ®Google Scholar
• Sia D, Hoshida Y, Villanueva A, et al. Integrative Molecular Analysis of Intrahepatic Cholangiocarcinoma Reveals 2 Classes That Have Different Outcomes. Gastroenterology. 2013;144(4):829–840.
   PubMed Web of Science ®Google Scholar
• Wardell CP, Fujita M, Yamada T, et al. Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations. J Hepatol. 2018;68(5):959–969.
   PubMed Web of Science ®Google Scholar
• Xue L, Guo C, Zhang K, et al. Comprehensive molecular profiling of extrahepatic cholangiocarcinoma in Chinese population and potential targets for clinical practice. Hepatobiliary Surg Nutr. 2019;8(6):615–622.
   PubMed Web of Science ®Google Scholar
• Montal R, Sia D, Montironi C, et al. Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma. J Hepatol. 2020;73(2):315–327.
   PubMed Web of Science ®Google Scholar
• Yang P, Javle M, Pang F, et al. Somatic genetic aberrations in gallbladder cancer: comparison between Chinese and US patients. Hepatobiliary Surg Nutr. 2019;8(6):604–614.
   PubMed Web of Science ®Google Scholar
• Maynard H, Stadler ZK, Berger MF, et al. Germline alterations in patients with biliary tract cancers: a spectrum of significant and previously underappreciated findings. Cancer. 2020;126(9):1995–2002.
   PubMed Web of Science ®Google Scholar
• Cao J, Hu J, Liu S, et al. Intrahepatic Cholangiocarcinoma: genomic Heterogeneity Between Eastern and Western Patients. JCO Precis Oncol. 2020;(4):557–569. DOI:10.1200/PO.18.00414
   Web of Science ®Google Scholar
• Jusakul A, Kongpetch S, Teh BT. Genetics of Opisthorchis viverrini-related cholangiocarcinoma. Curr Opin Gastroenterol. 2015;31(3):258–263.
   PubMed Web of Science ®Google Scholar
• Jusakul A, Cutcutache I, Yong CH, et al. Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma. Cancer Discov. 2017;7(10):1116–1135.
   PubMed Web of Science ®Google Scholar
• Chan-on W, Nairismägi M-L, Ong CK, et al. Exome sequencing identifies distinct mutational patterns in liver fluke–related and non-infection-related bile duct cancers. Nat Genet. 2013;45(12):1474–1478.
   PubMed Web of Science ®Google Scholar
• Cedar H, Bergman Y. Bergman Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009;10(5):295–304.
   PubMed Web of Science ®Google Scholar
• Goeppert B, Ernst C, Baer C, et al. Cadherin-6 is a putative tumor suppressor and target of epigenetically dysregulated miR-429 in cholangiocarcinoma. Epigenetics. 2016;11(11):780–790.
   PubMed Web of Science ®Google Scholar
• Braconi C, Huang N, Patel T. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology. 2010;51:NA–NA.
   Web of Science ®Google Scholar
• Chatterjee A, Rodger EJ, Eccles MR. Epigenetic drivers of tumourigenesis and cancer metastasis. Semin Cancer Biol. 2018;51:149–159.
   PubMed Web of Science ®Google Scholar
• Bergman Y, Cedar H. DNA methylation dynamics in health and disease. Nat Struct Mol Biol. 2013;20(3):274–281.
   PubMed Web of Science ®Google Scholar
• Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet. 2006;7(1):21–33.
   PubMed Web of Science ®Google Scholar
• Yang B, House MG, Guo M, et al. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma. Mod Pathol. 2005;18(3):412–420.
   PubMed Web of Science ®Google Scholar
• Losman JA, Kaelin WG. What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev. 2013;27(8):836–852.
   PubMed Web of Science ®Google Scholar
• Goeppert B, Toth R, Singer S, et al. Integrative Analysis Defines Distinct Prognostic Subgroups of Intrahepatic Cholangiocarcinoma. Hepatology. 2019;69(5):2091–2106.
   PubMed Web of Science ®Google Scholar
• Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(6):796–807.
   PubMed Web of Science ®Google Scholar
• Goeppert B, Konermann C, Schmidt CR, et al. Global alterations of DNA methylation in cholangiocarcinoma target the Wnt signaling pathway. Hepatology. 2014;59(2):544–554.
   PubMed Web of Science ®Google Scholar
• Isomoto H, Mott JL, Kobayashi S, et al. Sustained IL-6/STAT-3 Signaling in Cholangiocarcinoma Cells Due to SOCS-3 Epigenetic Silencing. Gastroenterology. 2007;132(1):384–396.
   PubMed Web of Science ®Google Scholar
• Andresen K, Boberg KM, Vedeld HM, et al. Novel target genes and a valid biomarker panel identified for cholangiocarcinoma. Epigenetics. 2012;7(11):1249–1257.
   PubMed Web of Science ®Google Scholar
• Kim Y, Lee K, Jeong S, et al. DLEC1 methylation is associated with a better clinical outcome in patients with intrahepatic cholangiocarcinoma of the small duct subtype. Virchows Arch. 2019;475(1):49–58.
   PubMed Web of Science ®Google Scholar
• Merino-Azpitarte M, Lozano E, Perugorria MJ, et al. SOX17 regulates cholangiocyte differentiation and acts as a tumor suppressor in cholangiocarcinoma. J Hepatol. 2017;67(1):72–83.
   PubMed Web of Science ®Google Scholar
• Morine Y, Shimada M, Iwahashi S, et al. role of histone deacetylase expression in intrahepatic cholangiocarcinoma. Surgery. 2012;151(3):412–419.
   PubMed Web of Science ®Google Scholar
• Pant K, Peixoto E, Richard S, et al. Role of Histone Deacetylases in Carcinogenesis: potential Role in Cholangiocarcinoma. Cells. 2020;9(3):780.
   PubMed Web of Science ®Google Scholar
• Iwahashi S, Shimada M, Utsunomiya T, et al. Histone deacetylase inhibitor enhances the anti-tumor effect of gemcitabine: a special reference to gene- expression microarray analysis. Oncol Rep. 2011;26(5):1057–1062.
   PubMed Web of Science ®Google Scholar
• Wang B, Yang R, Wu Y, et al. Sodium valproate inhibits the growth of human cholangiocarcinoma in vitro and in vivo. Gastroenterol Res Pract. 2013:2013. DOI:10.1155/2013/374593
   Web of Science ®Google Scholar
• Wang J, Lee E, Ji M, et al. HDAC inhibitors, trichostatin A and valproic acid, increase E‑cadherin and vimentin expression but inhibit migration and invasion of cholangiocarcinoma cells. Oncol Rep. 2018;40(1):346–354.
   PubMed Web of Science ®Google Scholar
• Jung DE, Park SB, Kim K, et al. CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway. Sci Rep. 2017;7(1):1–13.
   PubMed Web of Science ®Google Scholar
• Saha SK, Gordan JD, Kleinstiver BP, et al. Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma. Cancer Discov. 2016;6(7):727–739.
   PubMed Web of Science ®Google Scholar
• Lampis A, Carotenuto P, Vlachogiannis G, et al. MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma. Gastroenterology. 2018;154(4):1066–1079.e5.
   PubMed Web of Science ®Google Scholar
• Wasenang W, Puapairoj A, Settasatian C, et al. overexpression of polycomb repressive complex 2 key components EZH2/SUZ12/EED as an unfavorable prognostic marker in cholangiocarcinoma. Pathol Res Pract. 2019;215(7):152451.
   PubMed Web of Science ®Google Scholar
• Nakagawa S, Sakamoto Y, Okabe H, et al. Epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A inhibits the growth of cholangiocarcinoma cells. Oncol Rep. 2014;31(2):983–988.
   PubMed Web of Science ®Google Scholar
• Nakagawa S, Okabe H, Sakamoto Y, et al. Enhancer of Zeste Homolog 2 (EZH2) promotes progression of cholangiocarcinoma cells by regulating cell cycle and apoptosis. Ann Surg Oncol. 2013;20(S3):667–675.
   Web of Science ®Google Scholar
• Nakagawa S, Okabe H, Ouchi M, et al. Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma. Hpb. 2018;20(10):939–948.
   PubMed Web of Science ®Google Scholar
• Simbolo M, Fassan M, Ruzzenente A, et al. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups. Oncotarget. 2014;5(9):2839–2852.
   PubMedGoogle Scholar
• Yu H, Pak H, Hammond-Martel I, et al. Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci U S A. 2014;111(1):285–290.
   PubMed Web of Science ®Google Scholar
• Shen J, Peng Y, Wei L, et al. ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors. Cancer Discov. 2015;5(7):752–767.
   PubMed Web of Science ®Google Scholar
• Mao Y, Huang X, Shuang Z, et al. PARP inhibitor olaparib sensitizes cholangiocarcinoma cells to radiation. Cancer Med. 2018;7(4):1285–1296.
   PubMed Web of Science ®Google Scholar
• Braconi C, Roessler S, Kruk B, et al. Molecular perturbations in cholangiocarcinoma: is it time for precision medicine? Liver Int. 2019;39(Suppl 1):32–42.
   PubMed Web of Science ®Google Scholar
• Gradilone SA, O’Hara SP, Masyuk TV, et al. MicroRNAs and benign biliary tract diseases. Semin Liver Dis. 2015;35(1):26–35.
   PubMed Web of Science ®Google Scholar
• Mansini AP, Lorenzo Pisarello MJ, Thelen KM, et al. MicroRNA (miR)-433 and miR-22 dysregulations induce histone-deacetylase-6 overexpression and ciliary loss in cholangiocarcinoma. Hepatology. 2018;68(2):561–573.
   PubMed Web of Science ®Google Scholar
• Salati M, Braconi C. Noncoding RNA in Cholangiocarcinoma. Semin Liver Dis. 2019;39(1):13–25.
   PubMed Web of Science ®Google Scholar
• Wang J, Xie C, Pan S, et al. N-myc downstream-regulated gene 2 inhibits human cholangiocarcinoma progression and is regulated by leukemia inhibitory factor/MicroRNA-181c negative feedback pathway. Hepatology. 2016;64(5):1606–1622.
   PubMed Web of Science ®Google Scholar
• Zhu H, Mi Y, Jiang X, et al. Hepatocyte nuclear factor 6 inhibits the growth and metastasis of cholangiocarcinoma cells by regulating miR-122. J Cancer Res Clin Oncol. 2016;142(5):969–980.
   PubMed Web of Science ®Google Scholar
• Li J, Tian F, Li D, et al. MiR-605 represses PSMD10/Gankyrin and inhibits intrahepatic cholangiocarcinoma cell progression. FEBS Lett. 2014;588(18):3491–3500.
   PubMed Web of Science ®Google Scholar
• Jiang F, Ling X. The advancement of long non-coding RNAs in cholangiocarcinoma development. J Cancer. 2019;10(11):2407–2414.
   PubMed Web of Science ®Google Scholar
• Xu Y, Yao Y, Leng K, et al. Long non-coding RNA UCA1 indicates an unfavorable prognosis and promotes tumorigenesis via regulating AKT/GSK-3β signaling pathway in cholangiocarcinoma. Oncotarget. 2017;8(56):96203–96214.
   PubMedGoogle Scholar
• Zhang F, Wan M, Xu Y, et al. Transcriptome analysis reveals dysregulated long non-coding RNAs and mRNAs associated with extrahepatic cholangiocarcinoma progression. Oncol Lett. 2017;14(5):6079–6084.
   PubMed Web of Science ®Google Scholar
• Li J, Huang L, Li Z, et al. Functions and roles of long non-coding RNA in cholangiocarcinoma. J Cell Physiol. 2019;234(10):17113–17126.
   PubMed Web of Science ®Google Scholar
• Nakanuma Y, Uesaka K, Kakuda Y, et al. Intraductal Papillary Neoplasm of Bile Duct: updated Clinicopathological Characteristics and Molecular and Genetic Alterations. J Clin Med. 2020;9(12):3991.
   Web of Science ®Google Scholar
• Schlitter AM, Born D, Bettstetter M, et al. Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways. Mod Pathol. 2014;27(1):73–86.
   PubMed Web of Science ®Google Scholar
• Yang CY, Huang WJ, Tsai JH, et al. Targeted next-generation sequencing identifies distinct clinicopathologic and molecular entities of intraductal papillary neoplasms of the bile duct. Mod Pathol. 2019;32(11):1637–1645.
   PubMed Web of Science ®Google Scholar
• Aoki Y, Mizuma M, Hata T, et al. Intraductal papillary neoplasms of the bile duct consist of two distinct types specifically associated with clinicopathological features and molecular phenotypes. J Pathol. 2020;251(1):38–48.
   PubMed Web of Science ®Google Scholar
• Singhi AD, Wood LD, Parks E, et al. Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct. Gastroenterology. 2020;158(3):573–582.e2.
   PubMed Web of Science ®Google Scholar
• Goeppert B, Stichel D, Toth R, et al. Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis. Gut. gutjnl-2020-322983. 2021;gutjnl-2020-322983. DOI:10.1136/gutjnl-2020-322983
   PubMed Web of Science ®Google Scholar
• Itoh N, Ornitz DM. Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease. J Biochem. 2011;149(2):121–130.
   PubMed Web of Science ®Google Scholar
• Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10(2):116–129.
   PubMed Web of Science ®Google Scholar
• Gotoh N. Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins. Cancer Sci. 2008;99(7):1319–1325.
   PubMed Web of Science ®Google Scholar
• Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human cancer. Oncogene. 2005;24(50):7455–7464.
   PubMed Web of Science ®Google Scholar
• Klint P, Claesson-Welsh L. Signal transduction by fibroblast growth factor receptors. Front Biosci. 1999;4(1–3):165–177.
   PubMedGoogle Scholar
• Hart KC, Robertson SC, Kanemitsu MY, et al. Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4. Oncogene. 2000;19(29):3309–3320.
   PubMed Web of Science ®Google Scholar
• Kang S, Elf S, Dong S, et al. Fibroblast Growth Factor Receptor 3 Associates with and Tyrosine Phosphorylates p90 RSK2, Leading to RSK2 Activation That Mediates Hematopoietic Transformation. Mol Cell Biol. 2009;29(8):2105–2117.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Zhang Z-Y. The Mechanism of Dephosphorylation of Extracellular Signal-regulated Kinase 2 by Mitogen-activated Protein Kinase Phosphatase 3. J Biol Chem. 2001;276(34):32382–32391.
   PubMed Web of Science ®Google Scholar
• Casci T, Vinós J, Freeman M. Sprouty, an intracellular inhibitor of Ras signaling. Cell. 1999;96(5):655–665.
   PubMed Web of Science ®Google Scholar
• Hacohen N, Kramer S, Sutherland D, et al. sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell. 1998;92(2):253–263.
   PubMed Web of Science ®Google Scholar
• Fürthauer M, Lin W, Ang SL, et al. Sef is a feedback-induced antagonist of RAs/MAPK-mediated FGF signalling. Nat Cell Biol. 2002;4(2):170–174.
   PubMed Web of Science ®Google Scholar
• Tsang M, Friesel R, Kudoh T, et al. identification of sef, a novel modulator of FGF signalling. Nat Cell Biol. 2002;4(2):165–169.
   PubMed Web of Science ®Google Scholar
• Bekaii-Saab TS, Valle JW, Cutsem EV, et al. FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements. Futur Oncol. 2020;16(30):2385–2399.
   PubMed Web of Science ®Google Scholar
• Javle M, Lowery M, Shroff RT, et al. Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma. J Clin Oncol. 2017;36(3):276–282.
   PubMed Web of Science ®Google Scholar
• Makawita S, Abou-Alfa GK, Roychowdhury S, et al. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Futur Oncol. 2020;16(30):2375–2384.
   PubMed Web of Science ®Google Scholar
• Mazzaferro V, El-Rayes BF, Droz Dit Busset M, et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019;120(2):165–171.
   PubMed Web of Science ®Google Scholar
• Droz Dit Busset M, Braun S, El-Rayes B, et al. Efficacy of derazantinib (DZB) in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) expressing FGFR2-fusion or FGFR2 mutations/amplifications. Ann Oncol. 2019;30:v276–v277.
   Web of Science ®Google Scholar
• Chen -Y-Y, Park JO, Su W-C, et al. Preliminary results of a ph2a study to evaluate the clinical efficacy and safety of erdafitinib in Asian patients with biomarker-selected advanced cholangiocarcinoma (CCA). Ann Oncol. 2018;29:viii209.
   Web of Science ®Google Scholar
• Sootome H, Fujita H, Ito K, et al. Futibatinib Is a Novel Irreversible FGFR 1–4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors. Cancer Res. 2020;80(22):4986–4997.
   PubMed Web of Science ®Google Scholar
• Goyal L, Meric-Bernstam F, Hollebecque A, et al. FOENIX-CCA2: a phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements. J Clin Oncol. 2020;38(15_suppl):108.
   Web of Science ®Google Scholar
• Ng MCH, Goyal L, Bang Y-J, et al. AB065. P-36. Debio 1347 in patients with cholangiocarcinoma harboring an FGFR gene alteration: preliminary results. HepatoBiliary Surg Nutr. 2019;8(S1):AB065–AB065.
   Google Scholar
• Loriot Y, Necchi A, Park SH, et al. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019;381(4):338–348.
   PubMed Web of Science ®Google Scholar
• Salati M, Caputo F, Baldessari C, et al. IDH signalling pathway in cholangiocarcinoma: from biological rationale to therapeutic targeting. Cancers (Basel). 2020;12(11):1–11.
   Web of Science ®Google Scholar
• Grassian AR, Pagliarini R, Chiang DY. Mutations of isocitrate dehydrogenase 1 and 2 in intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol. 2014;30(3):295–302.
   PubMed Web of Science ®Google Scholar
• Saha SK, Parachoniak CA, Ghanta KS, et al. Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer. Nature. 2014;513(7516):110–114.
   PubMed Web of Science ®Google Scholar
• Borger DR, Goyal L, Yau T, et al. Circulating oncometabolite 2-Hydroxyglutarate Is a Potential Surrogate Biomarker in Patients with Isocitrate Dehydrogenase-Mutant Intrahepatic Cholangiocarcinoma. Clin Cancer Res. 2014;20(7):1884–1890.
   PubMed Web of Science ®Google Scholar
• Lowery MA, Abou-Alfa GK, Burris HA, et al. phase I study of AG-120, an IDH1 mutant enzyme inhibitor: results from the cholangiocarcinoma dose escalation and expansion cohorts. J Clin Oncol. 2017;35(15_suppl):4015.
   Google Scholar
• Subbiah V, Lassen U, Élez E, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020;21(9):1234–1243.
   PubMed Web of Science ®Google Scholar
• Mondaca S, Razavi P, Xu C, et al. Genomic characterization of ERBB2 -driven biliary cancer and a case of response to ado-trastuzumab emtansine. JCO Precis Oncol. 2019;3:PO.19.00223
   PubMed Web of Science ®Google Scholar
• Demols A, Borbath I, Van Den Eynde M, et al. Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial. Ann Oncol. 2020;31(9):1169–1177.
   PubMed Web of Science ®Google Scholar
• Knudsen ES, Witkiewicz AK. The strange case of CDK4/6 Inhibitors: mechanisms, resistance, and combination strategies. Trends Cancer. 2017;3(1):39–55.
   PubMed Web of Science ®Google Scholar
• Asghar U, Witkiewicz AK, Turner NC, et al. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov. 2015;14(2):130–146.
   PubMed Web of Science ®Google Scholar
• Hume S, Dianov GL, Ramadan K. A unified model for the G1/S cell cycle transition. Nucleic Acids Res. 2020;48(22):12483–12501.
   PubMed Web of Science ®Google Scholar
• Kato J, Matsushime H, Hiebert SW, et al. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993;7:331–342.
   PubMed Web of Science ®Google Scholar
• Sherr CJ. Cancer cell cycles. Science. 1996;274(80):1672–1674.
   PubMed Web of Science ®Google Scholar
• Burkhart DL, Sage J. Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cancer. 2008;8(9):671–682.
   PubMed Web of Science ®Google Scholar
• Tobias O, Piotr S. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer. 2017;17(2):93–115.
   PubMed Web of Science ®Google Scholar
• Bollard J, Miguela V, Ruiz De Galarreta M, et al. Palbociclib (PD-0332991), a selective CDK4/6 inhibitor, restricts tumour growth in preclinical models of hepatocellular carcinoma. Gut. 2017;66(7):1286–1296.
   PubMed Web of Science ®Google Scholar
• Song X, Liu X, Wang H, et al. Combined CDK4/6 and pan-mTOR inhibition is synergistic against intrahepatic cholangiocarcinoma. Clin Cancer Res. 2019;(1). DOI:10.1158/1078-0432.CCR-18-0284
   Web of Science ®Google Scholar
• Rugo HS, Diéras V, Gelmon KA, et al. Impact of palbociclib plus letrozole on patient-reported health-related quality of life: results from the PALOMA-2 trial. Ann Oncol. 2018;29(4):888–894.
   PubMed Web of Science ®Google Scholar
• Janni W, Alba E, Bachelot T, et al. First-line ribociclib plus letrozole in postmenopausal women with HR+, HER2− advanced breast cancer: tumor response and pain reduction in the phase 3 MONALEESA-2 trial. Breast Cancer Res Treat. 2018;169(3):469–479.
   PubMed Web of Science ®Google Scholar
• Johnston S, Martin M, Di Leo A, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019;5(1):1–8.
   PubMed Web of Science ®Google Scholar
• Flaherty KT, LoRusso PM, DeMichele A, et al. Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer. Clin Cancer Res. 2012;18(2):568–576.
   PubMed Web of Science ®Google Scholar
• Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004;3(11):1427–1437.
   PubMed Web of Science ®Google Scholar
• Gelbert LM, Cai S, Lin X, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014;32(5):825–837.
   PubMed Web of Science ®Google Scholar