Molecular Targets in Cholangiocarcinoma.
Bile Duct Neoplasms
/ drug therapy
Cholangiocarcinoma
/ drug therapy
Epigenome
ErbB Receptors
/ antagonists & inhibitors
Humans
Molecular Targeted Therapy
Receptor, Fibroblast Growth Factor, Type 2
/ antagonists & inhibitors
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Tumor Microenvironment
/ drug effects
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
05
03
2020
revised:
02
04
2020
accepted:
06
04
2020
pubmed:
19
4
2020
medline:
8
1
2022
entrez:
19
4
2020
Statut:
ppublish
Résumé
Cholangiocarcinoma (CCA) encompasses a heterogeneous collection of malignancies for which diagnostic biomarkers are lacking and population screening is infeasible because of its status as a rare disease. Coupled with high postsurgical recurrence rates among the minority of patients diagnosed at resectable stages, systemic clinical management will inevitably be required for the majority of patients with CCA with recurrent and advanced disease. In this review, we discuss the therapeutic potential of different classes of molecular targets at various stages of development in CCA, including those targeted to the tumor epithelia (oncogenic, developmental, metabolic, epigenomic) and tumor microenvironment (angiogenesis, checkpoint regulation). Furthermore, we discuss the successes and failures of CCA-targeted therapies, emphasizing key lessons learned that should pave the way for future molecular target evaluation in this uncommon yet bona fide target-rich disease.
Substances chimiques
ErbB Receptors
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 2
EC 2.7.10.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
62-74Informations de copyright
© 2020 by the American Association for the Study of Liver Diseases.
Références
Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P, 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.
Bertuccio P, Malvezzi M, Carioli G, Hashim D, Boffetta P, El-Serag HB, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol 2019;71:104-114.
Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273-1281.
Massard C, Michiels S, Ferte C, Le Deley MC, Lacroix L, Hollebecque A, et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov 2017;7:586-595.
Verlingue L, Malka D, Allorant A, Massard C, Ferte C, Lacroix L, et al. Precision medicine for patients with advanced biliary tract cancers: an effective strategy within the prospective MOSCATO-01 trial. Eur J Cancer 2017;87:122-130.
Goyal L, Saha SK, Liu LY, Siravegna G, Leshchiner I, Ahronian LG, et al. Polyclonal secondary FGFR2 mutations drive acquired resistance to FGFR inhibition in patients with FGFR2 fusion-positive cholangiocarcinoma. Cancer Discov 2017;7:252-263.
Nepal C, O'Rourke CJ, Oliveira D, Taranta A, Shema S, Gautam P, et al. Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma. Hepatology 2018;68:949-963.
Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol 2018;36:276-282.
Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol 2020;21:671-684.
Mazzaferro V, El-Rayes BF, Droz Dit Busset M, Cotsoglou C, Harris WP, Damjanov N, et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer 2019;120:165-171.
Krook MA, Bonneville R, Chen HZ, Reeser JW, Wing MR, Martin DM, et al. Tumor heterogeneity and acquired drug resistance in FGFR2-fusion-positive cholangiocarcinoma through rapid research autopsy. Cold Spring Harb Mol Case Stud 2019;5:a004002.
Goyal L, Shi L, Liu LY, Fece de la Cruz F, Lennerz JK, Raghavan S, et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma. Cancer Discov 2019;9:1064-1079.
Borad MJ, Bridgewater JA, Morizane C, Shroff RT, Oh D-Y, Moehler MH, et al. A phase III study of futibatinib (TAS-120) versus gemcitabine-cisplatin (gem-cis) chemotherapy as first-line (1L) treatment for patients (pts) with advanced (adv) cholangiocarcinoma (CCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene rearrangements (FOENIX-CCA3). J Clin Oncol 2020;38:TPS600.
Hollebecque A, Doi T, Saavedra O, Takahashi O, He H, Benhadji KA, et al. A phase II study of futibatinib (TAS-120) in patients (pts) with advanced (adv) solid tumors harboring fibroblast growth factor receptor (FGFR) genomic aberrations. J Clin Oncol 2020;38:TPS470.
Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-132.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25:1960-1966.
Chen JS, Hsu C, Chiang NJ, Tsai CS, Tsou HH, Huang SF, et al. A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer. Ann Oncol 2015;26:943-949.
Peck J, Wei L, Zalupski M, O'Neil B, Villalona Calero M, Bekaii-Saab T. HER2/neu may not be an interesting target in biliary cancers: results of an early phase II study with lapatinib. Oncology 2012;82:175-179.
Lee J, Park SH, Chang HM, Kim JS, Choi HJ, Lee MA, et al. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2012;13:181-188.
Javle M, Churi C, Kang HC, Shroff R, Janku F, Surapaneni R, et al. HER2/neu-directed therapy for biliary tract cancer. J Hematol Oncol 2015;8:58.
Yarlagadda B, Kamatham V, Ritter A, Shahjehan F, Kasi PM. Trastuzumab and pertuzumab in circulating tumor DNA ERBB2-amplified HER2-positive refractory cholangiocarcinoma. NPJ Precis Oncol 2019;3:19.
Riener MO, Bawohl M, Clavien PA, Jochum W. Rare PIK3CA hotspot mutations in carcinomas of the biliary tract. Genes Chromosomes Cancer 2008;47:363-367.
Bian JL, Wang MM, Tong EJ, Sun J, Li M, Miao ZB, et al. Benefit of everolimus in treatment of an intrahepatic cholangiocarcinoma patient with a PIK3CA mutation. World J Gastroenterol 2017;23:4311-4316.
Lau DK, Tay RY, Yeung YH, Chionh F, Mooi J, Murone C, et al. Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study. Br J Cancer 2018;118:966-971.
Buzzoni R, Pusceddu S, Bajetta E, De Braud F, Platania M, Iannacone C, et al. Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study. Ann Oncol 2014;25:1597-603.
Zhang S, Song X, Cao D, Xu Z, Fan B, Che L, et al. Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice. J Hepatol 2017;67:1194-1203.
Song X, Liu X, Wang H, Wang J, Qiao Y, Cigliano A, et al. Combined CDK4/6 and Pan-mTOR inhibition is synergistic against intrahepatic cholangiocarcinoma. Clin Cancer Res 2019;25:403-413.
Abou-Alfa GKMMT, Javle M, Kelley RK, Lubner S, Adeva J, et al. LBA10_PR ClarIDHy: a global, phase III, randomized, double-blind study of ivosidenib (IVO) vs placebo in patients with advanced cholangiocarcinoma (CC) with an isocitrate dehydrogenase 1 (IDH1) mutation. Ann Oncol 2019;30:v872-v873.
Vogel ASV, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, Paulson AS, et al. FIGHT-202: a phase 2 study of pemigatinib in patients (pts) with previously treated locally advanced or metastatic cholangiocarcinoma (CCA). Ann Oncol 2019;30:v851-v934.
Valle JW, Wasan H, Lopes A, Backen AC, Palmer DH, Morris K, et al. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial. Lancet Oncol 2015;16:967-978.
Cardinale V, Renzi A, Carpino G, Torrice A, Bragazzi MC, Giuliante F, et al. Profiles of cancer stem cell subpopulations in cholangiocarcinomas. Am J Pathol 2015;185:1724-1739.
Zong Y, Panikkar A, Xu J, Antoniou A, Raynaud P, Lemaigre F, et al. Notch signaling controls liver development by regulating biliary differentiation. Development 2009;136:1727-1739.
Zender S, Nickeleit I, Wuestefeld T, Sorensen I, Dauch D, Bozko P, et al. A critical role for notch signaling in the formation of cholangiocellular carcinomas. Cancer Cell 2013;23:784-795.
O'Rourke CJ, Matter MS, Nepal C, Caetano-Oliveira R, Ton PT, Factor VM, et al. Identification of a Pan-Gamma-secretase inhibitor response signature for Notch-driven cholangiocarcinoma. Hepatology 2020;71:196-213.
Guest RV, Boulter L, Dwyer BJ, Kendall TJ, Man TY, Minnis-Lyons SE, et al. Notch3 drives development and progression of cholangiocarcinoma. Proc Natl Acad Sci U S A 2016;113:12250-12255.
Huntzicker EG, Hotzel K, Choy L, Che L, Ross J, Pau G, et al. Differential effects of targeting Notch receptors in a mouse model of liver cancer. Hepatology 2015;61:942-952.
Gavai AV, Quesnelle C, Norris D, Han WC, Gill P, Shan W, et al. Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors. ACS Med Chem Lett 2015;6:523-7.
Massard C, Azaro A, Soria JC, Lassen U, Le Tourneau C, Sarker D, et al. First-in-human study of LY3039478, an oral Notch signaling inhibitor in advanced or metastatic cancer. Ann Oncol 2018;29:1911-1917.
Kummar S, O'Sullivan Coyne G, Do KT, Turkbey B, Meltzer PS, Polley E, et al. Clinical activity of the gamma-secretase inhibitor PF-03084014 in adults with desmoid tumors (aggressive fibromatosis). J Clin Oncol 2017;35:1561-1569.
Tolcher AW, Messersmith WA, Mikulski SM, Papadopoulos KP, Kwak EL, Gibbon DG, et al. Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. J Clin Oncol 2012;30:2348-2353.
Satriano L, Lewinska M, Rodrigues PM, Banales JM, Andersen JB. Metabolic rearrangements in primary liver cancers: cause and consequences. Nat Rev Gastroenterol Hepatol 2019;16:748-766.
Goeppert B, Toth R, Singer S, Albrecht T, Lipka DB, Lutsik P, et al. Integrative analysis defines distinct prognostic subgroups of intrahepatic cholangiocarcinoma. Hepatology 2019;69:2091-2106.
Lowery MA, Ptashkin R, Jordan E, Berger MF, Zehir A, Capanu M, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res 2018;24:4154-4161.
Wang P, Dong Q, Zhang C, Kuan PF, Liu Y, Jeck WR, et al. Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene 2013;32:3091-3100.
Farshidfar F, Zheng S, Gingras MC, Newton Y, Shih J, Robertson AG, et al. Integrative genomic analysis of cholangiocarcinoma identifies distinct IDH-mutant molecular profiles. Cell Rep 2017;19:2878-2880.
Jusakul A, Cutcutache I, Yong CH, Lim JQ, Huang MN, Padmanabhan N, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov 2017;7:1116-1135.
Saha SK, Parachoniak CA, Ghanta KS, Fitamant J, Ross KN, Najem MS, et al. Mutant IDH inhibits HNF-4alpha to block hepatocyte differentiation and promote biliary cancer. Nature 2014;513:110-114.
Saha SK, Gordan JD, Kleinstiver BP, Vu P, Najem MS, Yeo JC, et al. Isocitrate dehydrogenase mutations confer dasatinib hypersensitivity and SRC dependence in intrahepatic cholangiocarcinoma. Cancer Discov 2016;6:727-739.
Lowery MA, Burris HA 3rd, Janku F, Shroff RT, Cleary JM, Azad NS, et al. Safety and activity of ivosidenib in patients with IDH1-mutant advanced cholangiocarcinoma: a phase 1 study. Lancet Gastroenterol Hepatol 2019;4:711-720.
O'Rourke CJ, Lafuente-Barquero J, Andersen JB. Epigenome remodeling in cholangiocarcinoma. Trends Cancer 2019;5:335-350.
Chan-On W, Nairismagi ML, Ong CK, Lim WK, Dima S, Pairojkul C, et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet 2013;45:1474-1478.
Zou S, Li J, Zhou H, Frech C, Jiang X, Chu JS, et al. Mutational landscape of intrahepatic cholangiocarcinoma. Nat Commun 2014;5:5696.
Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, et al. Genomic spectra of biliary tract cancer. Nat Genet 2015;47:1003-1010.
Jiao Y, Pawlik TM, Anders RA, Selaru FM, Streppel MM, Lucas DJ, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet 2013;45:1470-1473.
Park Y, Chui MH, Suryo Rahmanto Y, Yu ZC, Shamanna RA, Bellani MA, et al. Loss of ARID1A in tumor cells renders selective vulnerability to combined ionizing radiation and PARP inhibitor therapy. Clin Cancer Res 2019;25:5584-5594.
Mao Y, Huang X, Shuang Z, Lin G, Wang J, Duan F, et al. PARP inhibitor olaparib sensitizes cholangiocarcinoma cells to radiation. Cancer Med 2018;7:1285-1296.
Wardell CP, Fujita M, Yamada T, Simbolo M, Fassan M, Karlic R, et al. Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations. J Hepatol 2018;68:959-969.
Dong LQ, Shi Y, Ma LJ, Yang LX, Wang XY, Zhang S, et al. Spatial and temporal clonal evolution of intrahepatic cholangiocarcinoma. J Hepatol 2018;69:89-98.
Artegiani B, van Voorthuijsen L, Lindeboom RGH, Seinstra D, Heo I, Tapia P, et al. Probing the tumor suppressor function of BAP1 in CRISPR-engineered human liver organoids. Cell Stem Cell 2019;24:927-943.e926.
Hogdall D, Lewinska M, Andersen JB. Desmoplastic tumor microenvironment and immunotherapy in cholangiocarcinoma. Trends Cancer 2018;4:239-255.
Ma L, Hernandez MO, Zhao Y, Mehta M, Tran B, Kelly M, et al. Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell 2019;36:418-430.e416.
Cadamuro M, Brivio S, Mertens J, Vismara M, Moncsek A, Milani C, et al. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma. J Hepatol 2019;70:700-709.
Lubner SJ, Mahoney MR, Kolesar JL, Loconte NK, Kim GP, Pitot HC, et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. J Clin Oncol 2010;28:3491-3497.
Yeh CN, Chang YC, Su Y, Shin-Shian Hsu D, Cheng CT, Wu RC, et al. Identification of MALT1 as both a prognostic factor and a potential therapeutic target of regorafenib in cholangiocarcinoma patients. Oncotarget 2017;8:113444-113459.
Sun W, Patel A, Normolle D, Patel K, Ohr J, Lee JJ, et al. A phase 2 trial of regorafenib as a single agent in patients with chemotherapy-refractory, advanced, and metastatic biliary tract adenocarcinoma. Cancer 2019;125:902-909.
Shroff RT, Yarchoan M, O'Connor A, Gallagher D, Zahurak ML, Rosner G, et al. The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma. Br J Cancer 2017;116:1402-1407.
Goyal L, Zheng H, Yurgelun MB, Abrams TA, Allen JN, Cleary JM, et al. A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma. Cancer 2017;123:1979-1988.
Job S, Rapoud D, Dos Santos A, Gonzalez P, Desterke C, Pascal G, et al. Identification of four immune subtypes characterized by distinct composition and functions of tumor microenvironment in intrahepatic cholangiocarcinoma. Hepatology 2019.
Goeppert B, Roessler S, Renner M, Singer S, Mehrabi A, Vogel MN, et al. Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma. Br J Cancer 2019;120:109-114.
Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, 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;38:1-10.
Zhou G, Sprengers D, Mancham S, Erkens R, Boor PPC, van Beek AA, et al. Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules. J Hepatol 2019;71:753-762.
Castven D, Becker D, Czauderna C, Wilhelm D, Andersen JB, Strand S, et al. Application of patient-derived liver cancer cells for phenotypic characterization and therapeutic target identification. Int J Cancer 2019;144:2782-2794.
Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarro LM, Bradshaw CR, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med 2017;23:1424-1435.
Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature 2019;575:217-223.
Corsello SMNR, Spangler RD, Rossen J, Kocak M, Bryan JG, Humeidi R, et al. Discovering the anticancer potential of non-oncology drugs by systematic viability profiling. Nat Cancer 2020;1:235-248.