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Perspective

Cholangiocarcinoma: bridging the translational gap from preclinical to clinical development and implications for future therapy

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Pages 365-375 | Received 18 Sep 2020, Accepted 19 Nov 2020, Published online: 08 Dec 2020

References

  • 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.
  • Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60:1268–1289.
  • Bertuccio P, Malvezzi M, Carioli G, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019;71(1):104–114.
  • Nakanuma Y, Kakuda Y. Pathologic classification of cholangiocarcinoma: new concepts. Best Pract Res Clin Gastroenterol. 2015;29(2):277–293.
  • 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.
  • Darwish Murad S, Kim WR, Harnois DM, et al. Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology. 2012;143:88–98e83. quiz e14
  • Fouassier L, Marzioni M, Afonso MB, et al. Signalling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance. Liver Int. 2019;39(Suppl 1):43–62.
  • Khan SA, Davidson BR, Goldin RD, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012;61(12):1657–1669.
  • Vicent S, Lieshout R, Saborowski A, et al. Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholangiocarcinoma. Liver Int. 2019;39(Suppl 1):79–97.
  • Mirabelli P, Coppola L, Salvatore M. Cancer cell lines are useful model systems for medical research. Cancers (Basel). 2019;11(8):1098.
  • Costa EC, Moreira AF, de Melo-diogo D, et al. 3D tumor spheroids: an overview on the tools and techniques used for their analysis. Biotechnol Adv. 2016;34(8):1427–1441.
  • Cardinale V, Renzi A, Carpino G, et al. Profiles of cancer stem cell subpopulations in cholangiocarcinomas. Am J Pathol. 2015;185(6):1724–1739.
  • Di Matteo S, Nevi L, Costantini D, et al. The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma. PLoS One. 2019;14(1):e0210077.
  • Mischiati C, Ura B, Roncoroni L, et al. Changes in protein expression in two cholangiocarcinoma cell lines undergoing formation of multicellular tumor spheroids in vitro. PLoS One. 2015;10(3):e0118906.
  • Huch M, Koo BK. Modeling mouse and human development using organoid cultures. Development. 2015;142(18):3113–3125.
  • Huch M, Gehart H, van Boxtel R, et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell. 2015;160(1–2):299–312.
  • Broutier L, Mastrogiovanni G, Verstegen MM, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 2017;23(12):1424–1435.
  • Amato F, Rae C, Prete MG, et al. Cholangiocarcinoma disease modelling through patients derived organoids. Cells. 2020;9(4):832.
  • Loeuillard E, Fischbach SR, Gores GJ, et al. Animal models of cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis. 2019;1865(5):982–992.
  • Mohr R, Ozdirik B, Knorr J, et al. In Vivo models for cholangiocarcinoma—what can we learn for human disease? Int J Mol Sci. 2020;21(14):4993.
  • Massa A, Varamo C, Vita F, et al. Evolution of the experimental models of cholangiocarcinoma. Cancers (Basel). 2020;12(8):2308.
  • Primrose JN, Fox RP, Palmer DH, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20(5):663–673.
  • Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–1281.
  • Hezel AF, Deshpande V, Zhu AX. Genetics of biliary tract cancers and emerging targeted therapies. J Clin Oncol. 2010;28(21):3531–3540.
  • Massironi S, Pilla L, Elvevi A, et al. New and emerging systemic therapeutic options for advanced cholangiocarcinoma. Cells. 2020;9 (3):688.
  • Liu Y, Lang F, Chou FJ, et al. Isocitrate dehydrogenase mutations in glioma: genetics, biochemistry, and clinical indications. Biomedicines. 2020;9 (9):294.
  • Waitkus MS, Diplas BH, Yan H. Biological role and therapeutic potential of IDH mutations in cancer. Cancer Cell. 2018;34(2):186–195.
  • Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462(7274):739–744.
  • Golub D, Iyengar N, Dogra S, et al. Mutant isocitrate dehydrogenase inhibitors as targeted cancer therapeutics. Front Oncol. 2019;9:417.
  • Moeini A, Sia D, Bardeesy N, et al. Molecular pathogenesis and targeted therapies for intrahepatic cholangiocarcinoma. Clin Cancer Res. 2016;22(2):291–300.
  • 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.
  • Itoh N, Ornitz DM. Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease. J Biochem. 2011;149(2):121–130.
  • Babina IS, Turner NC. Advances and challenges in targeting FGFR signalling in cancer. Nat Rev Cancer. 2017;17(5):318–332.
  • Wu YM, Su F, Kalyana-Sundaram S, et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013;3(6):636–647.
  • Arai Y, Totoki Y, Hosoda F, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59(4):1427–1434.
  • Yoo C, Kang J, Kim D, et al. Multiplexed gene expression profiling identifies the FGFR4 pathway as a novel biomarker in intrahepatic cholangiocarcinoma. Oncotarget. 2017;8(24):38592–38601.
  • Javle M, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36(3):276–282.
  • Goyal L, Saha SK, Liu LY, et al. Polyclonal secondary FGFR2 mutations drive acquired resistance to FGFR inhibition in patients with FGFR2 fusion–positive cholangiocarcinoma. Cancer Discov. 2017;7(3):252–263.
  • Bahleda R, Italiano A, Hierro C, et al. Multicenter phase I study of erdafitinib (JNJ-42756493), oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced or refractory solid tumors. Clin Cancer Res. 2019;25(16):4888–4897.
  • Hall TG, Yu Y, Eathiraj S, et al. Preclinical activity of ARQ 087, a novel inhibitor targeting FGFR dysregulation. PLoS One. 2016;11(9):e0162594.
  • Raggi C, Fiaccadori K, Pastore M, et al. Antitumor activity of a novel fibroblast growth factor receptor inhibitor for intrahepatic cholangiocarcinoma. Am J Pathol. 2019;189(10):2090–2101.
  • 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.
  • Goyal L, Shi L, Liu LY, et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma. Cancer Discov. 2019;9(8):1064–1079.
  • Voss MH, Hierro C, Heist RS, et al. A phase I, open-label, multicenter, dose-escalation study of the oral selective FGFR inhibitor Debio 1347 in patients with advanced solid tumors harboring FGFR gene alterations. Clin Cancer Res. 2019;25(9):2699–2707.
  • Bekaii-Saab TS, Valle JW, Cutsem EV, et al. FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements. Future Oncol. 2020;16(30):2385–2399.
  • Makawita S, KA-A G, Roychowdhury S, et al. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Future Oncol. 2020. DOI:10.2217/fon-2020-0299.
  • Javle M, Churi C, Kang HC, et al. HER2/neu-directed therapy for biliary tract cancer. J Hematol Oncol. 2015;8(1):58.
  • Lindsey S, Langhans SA. Epidermal growth factor signaling in transformed cells. Int Rev Cell Mol Biol. 2015;314:1–41.
  • Galdy S, Lamarca A, McNamara MG, et al. HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target? Cancer Metastasis Rev. 2017;36(1):141–157.
  • Zhang Z, Oyesanya RA, Campbell DJ, et al. Preclinical assessment of simultaneous targeting of epidermal growth factor receptor (ErbB1) and ErbB2 as a strategy for cholangiocarcinoma therapy. Hepatology. 2010;52(3):975–986.
  • Pignochino Y, Sarotto I, Peraldo-Neia C, et al. Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas. BMC Cancer. 2010;10(1):631.
  • Peck J, Wei L, Zalupski M, et al. HER2/neu may not be an interesting target in biliary cancers: results of an early phase II study with lapatinib. Oncology. 2012;82(3):175–179.
  • Ramanathan RK, Belani CP, Singh DA, et al. A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother Pharmacol. 2009;64(4):777–783.
  • Andersen JB, Spee B, Blechacz BR, et al. Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors. Gastroenterology. 2012;142(4):1021–1031 e1015.
  • Canon J, Rex K, Saiki AY, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019;575:217–223.
  • Bekaii-Saab T, Phelps MA, Li X, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol. 2011;29(17):2357–2363.
  • Goeppert B, Frauenschuh L, Renner M, et al. BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma. Mod Pathol. 2014;27(7):1028–1034.
  • Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015;373:726–736.
  • Lavingia V, Fakih M. Impressive response to dual BRAF and MEK inhibition in patients with BRAF mutant intrahepatic cholangiocarcinoma-2 case reports and a brief review. J Gastrointest Oncol. 2016;7(7):E98–E102.
  • Subbiah V, Lassen U, Elez E, et al. Dabrafenib plus trametinib in patients with BRAF(V600E)-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020;21(9):1234–1243.
  • Gu TL, Deng X, Huang F, et al. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma. PLoS One. 2011;6:e15640.
  • Saborowski A, Saborowski M, Davare MA, et al. Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target. Proc Natl Acad Sci U S A. 2013;110:19513–19518.
  • Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020;10:727–742.
  • Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98–106.
  • Nakamura H, Arai Y, Totoki Y, et al. Genomic spectra of biliary tract cancer. Nat Genet. 2015;47(9):1003–1010.
  • Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–413.
  • Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(1):1–10.
  • Ahn S, Lee JC, Shin DW, et al. High PD-L1 expression is associated with therapeutic response to pembrolizumab in patients with advanced biliary tract cancer. Sci Rep. 2020;10(1):12348.
  • Kim RD, Chung V, Alese OB, et al. A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer. JAMA Oncol. 2020;6(6):888–894.
  • Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Exp Clin Cancer Res. 2019;38(1):255.
  • Kanno N, LeSage G, Glaser S, et al. Regulation of cholangiocyte bicarbonate secretion. Am J Physiol Gastrointest Liver Physiol. 2001;281:G612–625.
  • Mancinelli R, Franchitto A, Gaudio E, et al. After damage of large bile ducts by gamma-aminobutyric acid, small ducts replenish the biliary tree by amplification of calcium-dependent signaling and de novo acquisition of large cholangiocyte phenotypes. Am J Pathol. 2010;176(4):1790–1800.
  • Korner M, Hayes GM, Rehmann R, et al. Secretin receptors in the human liver: expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma. J Hepatol. 2006;45(6):825–835.
  • Onori P, Wise C, Gaudio E, et al. Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP-dependent signaling mechanisms of secretin receptor. Int J Cancer. 2010;127:43–54.
  • Wu N, Baiocchi L, Zhou T, et al. The functional role of the secretin/secretin receptor signaling during cholestatic liver injury. Hepatology. 2020. DOI:10.1002/hep.31484.
  • Tietz PS, Alpini G, Pham LD, et al. Somatostatin inhibits secretin-induced ductal hypercholeresis and exocytosis by cholangiocytes. Am J Physiol. 1995;269:G110–118.
  • Tan CK, Podila PV, Taylor JE, et al. Human cholangiocarcinomas express somatostatin receptors and respond to somatostatin with growth inhibition. Gastroenterology. 1995;108(6):1908–1916.
  • Fiebiger WC, Scheithauer W, Traub T, et al. Absence of therapeutic efficacy of the somatostatin analogue lanreotide in advanced primary hepatic cholangiocellular cancer and adenocarcinoma of the gallbladder despite in vivo somatostatin-receptor expression. Scand J Gastroenterol. 2002;37(2):222–225.
  • Han Y, DeMorrow S, Invernizzi P, et al. Melatonin exerts by an autocrine loop antiproliferative effects in cholangiocarcinoma: its synthesis is reduced favoring cholangiocarcinoma growth. Am J Physiol Gastrointest Liver Physiol. 2011;301:G623–633.
  • Han Y, Meng F, Venter J, et al. miR-34a-dependent overexpression of Per1 decreases cholangiocarcinoma growth. J Hepatol. 2016;64(6):1295–1304.
  • Pencik J, Pham HT, Schmoellerl J, et al. JAK-STAT signaling in cancer: from cytokines to non-coding genome. Cytokine. 2016;87:26–36.
  • 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.
  • Yoshikawa D, Ojima H, Iwasaki M, et al. Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma. Br J Cancer. 2008;98(2):418–425.
  • Vaeteewoottacharn K, Kariya R, Dana P, et al. Inhibition of carbonic anhydrase potentiates bevacizumab treatment in cholangiocarcinoma. Tumour Biol. 2016;37(7):9023–9035.
  • Zhu AX, Meyerhardt JA, Blaszkowsky LS, et al. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol. 2010;11(1):48–54.
  • Sato K, Meng F, Glaser S, et al. Exosomes in liver pathology. J Hepatol. 2016;65(1):213–221.
  • Liu T, Yang H, Fan W, et al. Mechanisms of MAFG dysregulation in cholestatic liver injury and development of liver cancer. Gastroenterology. 2018;155(2):557–571 e514.
  • van der Laan AL, Boenink M. Beyond bench and bedside: disentangling the concept of translational research. Health Care Anal. 2015;23(1):32–49.
  • Kendall T, Verheij J, Gaudio E, et al. Anatomical, histomorphological and molecular classification of cholangiocarcinoma. Liver Int. 2019;39(Suppl 1):7–18.
  • Wang Y, Ding X, Wang S, et al. Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein. Cancer Lett. 2016;380(1):163–173.
  • Saha SK, Parachoniak CA, Ghanta KS, et al. Corrigendum: mutant IDH inhibits HNF-4alpha to block hepatocyte differentiation and promote biliary cancer. Nature. 2015;528(7580):152.
  • Fabris L, Sato K, Alpini G, et al. The tumor microenvironment in cholangiocarcinoma progression. Hepatology. 2020. DOI:10.1002/hep.31410.
  • Patel T. Cholangiocarcinoma–controversies and challenges. Nat Rev Gastroenterol Hepatol. 2011;8:189–200.
  • Marin JJG, Lozano E, Herraez E, et al. Chemoresistance and chemosensitization in cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis. 2018;1864(4):1444–1453.
  • Friedman AA, Letai A, Fisher DE, et al. Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. 2015;15:747–756.
  • Boyd LNC, Peters GJ, Kazemier G, et al. NUC-1031 in biliary tract cancer: from bench to bedside and back? Cancer Chemother Pharmacol. 2020;85(6):1011–1014.
  • Arora M, Bogenberger JM, Abdelrahman A, et al. Evaluation of NUC-1031: a first-in-class ProTide in biliary tract cancer. Cancer Chemother Pharmacol. 2020;85(6):1063–1078.
  • 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.
  • Tepsiri N, Chaturat L, Sripa B, et al. Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines. World J Gastroenterol. 2005;11(18):2748–2753.

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