{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T14:07:21Z","timestamp":1764079641308,"version":"build-2065373602"},"reference-count":144,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Cancer Research, National Health Research Institutes; Chang Gung Memorial Hospital","award":["CA-109-PP-23 (NJC); CORPG 3J0251~2, CMRPG 3I0241~2, CRRPG 3K0011, CRRPG 3K0031, CMRPG 3K0711 (CNY)"],"award-info":[{"award-number":["CA-109-PP-23 (NJC); CORPG 3J0251~2, CMRPG 3I0241~2, CRRPG 3K0011, CRRPG 3K0031, CMRPG 3K0711 (CNY)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Biliary tract cancer (BTC) compromises a heterogenous group of tumors with poor prognoses. Curative surgery remains the first choice for localized disease; however, most BTC patients have had unresectable or metastatic disease. The gold standard therapy for these patients is chemotherapy with gemcitabine and cisplatin. There are no consensus guidelines for standard treatment in a second-line setting, although the data of the ABC-06 trial showed a slight survival benefit from oxaliplatin and 5-fluorouracil combination chemotherapy. Recent progress in comprehensive genomic profiling for advanced BTC (ABTC) has helped to clarify tumorigenesis and facilitate the coming era of precision medicine. Generally, targeted agents fail to show significant clinical benefits in unselected populations. Only fibroblast growth factor receptor 2 (FGFR2) fusion and isocitrate dehydrogenase (IDH)- and BRAF mutation-enriched populations have survival benefits from the corresponding inhibitors. Several interesting targeted agents for monotherapies or combination therapies with other compounds are currently ongoing or recruiting. Here, we review the published data from clinical trials of second-line therapies after the failure of gemcitabine-based chemotherapy in ABTC. The results were stratified by different genetic alternations, as well as by chemotherapy, targeted therapy and immunotherapy.<\/jats:p>","DOI":"10.3390\/biom11010097","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T11:52:32Z","timestamp":1610538752000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials"],"prefix":"10.3390","volume":"11","author":[{"given":"Nai-Jung","family":"Chiang","sequence":"first","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan"},{"name":"Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Tzong","family":"Chen","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan"},{"name":"Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Shen","family":"Shan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Department of Surgery, National Cheng Kung University Hospital, Tainan 704, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1455-092X","authenticated-orcid":false,"given":"Chun-Nan","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-7393","authenticated-orcid":false,"given":"Ming-Huang","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan"},{"name":"School of Medicine, National Yang Ming University, Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.2147\/CMAR.S157092","article-title":"Biliary tract cancers: Current knowledge, clinical candidates and future challenges","volume":"11","author":"Tariq","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrgastro.2016.51","article-title":"Cholangiocarcinoma: Current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)","volume":"13","author":"Banales","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1159\/000453013","article-title":"Epidemiology and Risk Factors of Cholangiocarcinoma","volume":"32","author":"Kirstein","year":"2016","journal-title":"Visc. Med."},{"key":"ref_4","first-page":"21","article-title":"Cholangiocarcinoma: Epidemiology and risk factors","volume":"1","author":"Bragazzi","year":"2011","journal-title":"Transl. Gastrointest. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.21037\/tgh.2018.07.02","article-title":"Precision medicine in cholangiocarcinoma","volume":"3","author":"Pellino","year":"2018","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.cgh.2017.09.031","article-title":"Effect of Nucleos(t)ide Analogue Therapy on Risk of Intrahepatic Cholangiocarcinoma in Patients With Chronic Hepatitis B","volume":"16","author":"Lee","year":"2018","journal-title":"Clin Gastroenterol Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/sj.bjc.6605779","article-title":"Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: A comparative multicentre study in Japan","volume":"103","author":"Okusaka","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","article-title":"Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer","volume":"362","author":"Valle","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1093\/annonc\/mdz402","article-title":"Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced\/recurrent biliary tract cancer: The FUGA-BT (JCOG1113) randomized phase III clinical trial","volume":"30","author":"Morizane","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1111\/cas.12218","article-title":"Randomized phase II study of gemcitabine plus S-1 versus S-1 in advanced biliary tract cancer: A Japan Clinical Oncology Group trial (JCOG 0805)","volume":"104","author":"Morizane","year":"2013","journal-title":"Cancer Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"viii205","DOI":"10.1093\/annonc\/mdy282","article-title":"Randomized phase III study of gemcitabine, cisplatin plus S-1 (GCS) versus gemcitabine, cisplatin (GC) for advanced biliary tract cancer (KHBO1401-MITSUBA)","volume":"29","author":"Sakai","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1038\/bjc.2014.190","article-title":"Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer","volume":"110","author":"Fornaro","year":"2014","journal-title":"Br. J. Cancer."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1056\/NEJMoa0805019","article-title":"Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer","volume":"360","author":"Kohne","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1093\/annonc\/mdu162","article-title":"Second-line chemotherapy in advanced biliary cancer: A systematic review","volume":"25","author":"Lamarca","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.jhep.2018.01.009","article-title":"Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations","volume":"68","author":"Wardell","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Krook, M.A., Lenyo, A., Wilberding, M., Barker, H., Dantuono, M., Bailey, K.M., Chen, H.-Z., Reeser, J.W., Wing, M.R., and Miya, J. (2020). Efficacy of FGFR inhibitors and combination therapies for acquired resistance in FGFR2-fusion cholangiocarcinoma. Mol. Cancer Ther.","DOI":"10.1158\/1538-7445.SABCS18-335"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jhep.2020.03.007","article-title":"Molecular targeted therapies: Ready for prime time in biliary tract cancer","volume":"73","author":"Lamarca","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jhep.2017.03.026","article-title":"Emerging molecular therapeutic targets for cholangiocarcinoma","volume":"67","author":"Rizvi","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/MOG.0000000000000162","article-title":"Genetics of Opisthorchis viverrini-related cholangiocarcinoma","volume":"31","author":"Jusakul","year":"2015","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cao, J., Hu, J., Liu, S., Meric-Bernstam, F., Abdel-Wahab, R., Xu, J., Li, Q., Yan, M., Feng, Y., and Lin, J. (2020). Intrahepatic Cholangiocarcinoma: Genomic Heterogeneity Between Eastern and Western Patients. JCO Precis. Oncol., 557\u2013569.","DOI":"10.1200\/PO.18.00414"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.critrevonc.2019.01.001","article-title":"Combination versus mono-therapy as salvage treatment for advanced biliary tract cancer: A comprehensive meta-analysis of published data","volume":"139","author":"Ying","year":"2019","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1200\/JCO.2019.37.15_suppl.4003","article-title":"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-treated with cisplatin\/gemcitabine (CisGem) chemotherapy","volume":"37","author":"Lamarca","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3290","DOI":"10.1002\/cncr.29471","article-title":"Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Ent\u00e9rologues Oncologues","volume":"121","author":"Brieau","year":"2015","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1007\/s00280-013-2106-0","article-title":"A multicenter phase II study of S-1 for gemcitabine-refractory biliary tract cancer","volume":"71","author":"Suzuki","year":"2013","journal-title":"Cancer Chemother Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"909","DOI":"10.21873\/anticanres.11398","article-title":"A Multicenter Phase II Study of Gemcitabine plus S-1 Chemotherapy for Advanced Biliary Tract Cancer","volume":"37","author":"Arima","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1159\/000479970","article-title":"Efficacy and Safety of Capecitabine, Irinotecan, Gemcitabine, and Bevacizumab as Second-Line Treatment in Advanced Biliary Tract Cancer: A Phase II Study","volume":"94","author":"Larsen","year":"2018","journal-title":"Oncology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/s41416-019-0698-9","article-title":"Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: An open-label, single arm, phase 2 trial","volume":"122","author":"Belkouz","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1200\/jco.2015.33.3_suppl.463","article-title":"Nab-paclitaxel as second-line treatment in advanced biliary cancer","volume":"33","author":"Prager","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1158\/2159-8290.CD-17-0245","article-title":"New Horizons for Precision Medicine in Biliary Tract Cancers","volume":"7","author":"Valle","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1002\/hep.26890","article-title":"Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma","volume":"59","author":"Arai","year":"2014","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/s12967-020-02437-2","article-title":"Comprehensive molecular profiling of intrahepatic cholangiocarcinoma in the Chinese population and therapeutic experience","volume":"18","author":"Wang","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.humpath.2014.03.014","article-title":"Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma","volume":"45","author":"Graham","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jain, A., Borad, M.J., Kelley, R.K., Wang, Y., Abdel-Wahab, R., Meric-Bernstam, F., Baggerly, K.A., Kaseb, A.O., Al-shamsi, H.O., and Ahn, D.H. (2018). Cholangiocarcinoma With FGFR Genetic Aberrations: A Unique Clinical Phenotype. JCO Precis. Oncol., 1\u201312.","DOI":"10.1200\/PO.17.00080"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1470-2045(20)30109-1","article-title":"Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: A multicentre, open-label, phase 2 study","volume":"21","author":"Sahai","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_35","unstructured":"(2020, May 11). U.S. Food and Drug Administration: FDA Grants Accelerated Approval to Pemigatinib for Cholangiocarcinoma with an FGFR2 Rearrangement or Fusion, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-grants-accelerated-approval-pemigatinib-cholangiocarcinoma-fgfr2-rearrangement-or-fusion."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1200\/JCO.2017.75.5009","article-title":"Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma","volume":"36","author":"Javle","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"viii720","DOI":"10.1093\/annonc\/mdy424.030","article-title":"Updated results from a phase II study of infigratinib (BGJ398), a selective pan-FGFR kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma containing FGFR2 fusions","volume":"29","author":"Javle","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41416-018-0334-0","article-title":"Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma","volume":"120","author":"Mazzaferro","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1158\/2159-8290.CD-19-0182","article-title":"TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion\u2013Positive Intrahepatic Cholangiocarcinoma","volume":"9","author":"Goyal","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"ix49","DOI":"10.1093\/annonc\/mdy432.007","article-title":"Efficacy of TAS-120, an irreversible fibroblast growth factor receptor inhibitor (FGFRi), in patients with cholangiocarcinoma and FGFR pathway alterations previously treated with chemotherapy and other FGFRi\u2019s","volume":"29","author":"Tran","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1158\/1078-0432.CCR-18-3334","article-title":"Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors","volume":"25","author":"Bahleda","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"v876","DOI":"10.1093\/annonc\/mdz394.031","article-title":"FIGHT-202: A phase II study of pemigatinib in patients (pts) with previously treated locally advanced or metastatic cholangiocarcinoma (CCA)","volume":"30","author":"Vogel","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1681\/ASN.2007010068","article-title":"How fibroblast growth factor 23 works","volume":"18","author":"Liu","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1002\/jbmr.478","article-title":"FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone","volume":"26","author":"Bonny","year":"2011","journal-title":"J. Bone Min. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1002\/jbmr.1810","article-title":"Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets","volume":"28","author":"Henninger","year":"2013","journal-title":"J. Bone Min. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2147\/JBM.S70716","article-title":"IDH1 and IDH2 mutations as novel therapeutic targets: Current perspectives","volume":"7","author":"Mondesir","year":"2016","journal-title":"J. Blood Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3389\/fgene.2018.00493","article-title":"IDH1: Linking Metabolism and Epigenetics","volume":"9","author":"Raineri","year":"2018","journal-title":"Front. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"430","DOI":"10.21037\/jgo.2017.05.04","article-title":"Current biologics for treatment of biliary tract cancers","volume":"8","author":"Zhao","year":"2017","journal-title":"J. Gastrointest Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"751","DOI":"10.21037\/jgo.2019.03.10","article-title":"Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: A systematic literature review","volume":"10","author":"Boscoe","year":"2019","journal-title":"J. Gastrointest Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S1470-2045(20)30157-1","article-title":"Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): A multicentre, randomised, double-blind, placebo-controlled, phase 3 study","volume":"21","author":"Macarulla","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.currproblcancer.2010.12.002","article-title":"PARP inhibitor treatment in ovarian and breast cancer","volume":"35","author":"Weil","year":"2011","journal-title":"Curr. Probl. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yap, T.A., Plummer, R., Azad, N.S., and Helleday, T. (2019). The DNA Damaging Revolution: PARP Inhibitors and Beyond. Am. Soc. Clin. Oncol. Educ. Book, 185\u2013195.","DOI":"10.1200\/EDBK_238473"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ejca.2019.07.022","article-title":"Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer: DNA damage repair gene mutations as a predictive biomarker","volume":"120","author":"Chae","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Heeke, A.L., Pishvaian, M.J., Lynce, F., Xiu, J., Brody, J.R., Chen, W.-J., Baker, T.M., Marshall, J.L., and Isaacs, C. (2018). Prevalence of Homologous Recombination-Related Gene Mutations Across Multiple Cancer Types. JCO Precis. Oncol., 2018.","DOI":"10.1200\/PO.17.00286"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1634\/theoncologist.2016-0415","article-title":"Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective Study","volume":"22","author":"Golan","year":"2017","journal-title":"Oncologist"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11864-016-0432-2","article-title":"Genomic Profiling of Biliary Tract Cancers and Implications for Clinical Practice","volume":"17","author":"Jain","year":"2016","journal-title":"Curr Treat Options Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e000682","DOI":"10.1136\/esmoopen-2020-000682","article-title":"Molecular profile of BRCA-mutated biliary tract cancers","volume":"5","author":"Spizzo","year":"2020","journal-title":"ESMO Open"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eaal2463","DOI":"10.1126\/scitranslmed.aal2463","article-title":"2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity","volume":"9","author":"Sulkowski","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12851","DOI":"10.1073\/pnas.1817662116","article-title":"2-hydroxyglutarate inhibits MyoD-mediated differentiation by preventing H3K9 demethylation","volume":"116","author":"Schvartzman","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Pignochino, Y., Sarotto, I., Peraldo-Neia, C., Penachioni, J.Y., Cavalloni, G., Migliardi, G., Casorzo, L., Chiorino, G., Risio, M., and Bardelli, A. (2010). Targeting EGFR\/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-631"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1093\/annonc\/mds008","article-title":"Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer","volume":"23","author":"Jensen","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1200\/JCO.2005.05.3579","article-title":"Phase II study of erlotinib in patients with advanced biliary cancer","volume":"24","author":"Philip","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_63","first-page":"13-e23","article-title":"Phase II Trial of Erlotinib and Docetaxel in Advanced and Refractory Hepatocellular and Biliary Cancers: Hoosier Oncology Group GI06-101","volume":"17","author":"Chiorean","year":"2012","journal-title":"Oncology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00432-005-0016-1","article-title":"Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas","volume":"131","author":"Gwak","year":"2005","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1158\/1078-0432.CCR-05-1692","article-title":"Somatic Mutations of Epidermal Growth Factor Receptor in Bile Duct and Gallbladder Carcinoma","volume":"12","author":"Leone","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1158\/1078-0432.CCR-17-0432","article-title":"Phase I Study of Chimeric Antigen Receptor\u2013Modified T Cells in Patients with EGFR-Positive Advanced Biliary Tract Cancers","volume":"24","author":"Guo","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"55","DOI":"10.5858\/2010-0454-RAR.1","article-title":"HER2: Biology, detection, and clinical implications","volume":"135","author":"Gutierrez","year":"2011","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41571-019-0268-3","article-title":"HER2-targeted therapies\u2014A role beyond breast cancer","volume":"17","author":"Oh","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13045-015-0155-z","article-title":"HER2\/neu-directed therapy for biliary tract cancer","volume":"8","author":"Javle","year":"2015","journal-title":"J. Hematol. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1200\/JCO.2017.35.4_suppl.402","article-title":"Pertuzumab + trastuzumab for HER2-positive metastatic biliary cancer: Preliminary data from MyPathway","volume":"35","author":"Javle","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nature25475","article-title":"HER kinase inhibition in patients with HER2- and HER3-mutant cancers","volume":"554","author":"Hyman","year":"2018","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"iv127","DOI":"10.1093\/annonc\/mdz154.004","article-title":"Treating HER2-mutant advanced biliary tract cancer with neratinib: Benefits of HER2-directed targeted therapy in the phase 2 SUMMIT \u2018basket\u2019 trial","volume":"30","author":"Harding","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1200\/JCO.2019.37.4_suppl.331","article-title":"Efficacy and safety of varlitinib, a reversible pan-HER tyrosine kinase inhibitor, in combination with platinum-based regimens in biliary tract cancers: A pooled analysis from three phase I studies","volume":"37","author":"Tan","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s00280-009-0927-7","article-title":"A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer","volume":"64","author":"Ramanathan","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1200\/JCO.2020.38.15_suppl.4597","article-title":"Results from TreeTopp: A randomized phase II study of the efficacy and safety of varlitinib plus capecitabine versus placebo in second-line (2L) advanced or metastatic biliary tract cancer (BTC)","volume":"38","author":"Javle","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1007\/s13238-017-0440-4","article-title":"Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers","volume":"9","author":"Feng","year":"2018","journal-title":"Protein Cell."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1158\/2159-8290.CD-19-1014","article-title":"Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors","volume":"10","author":"Tsurutani","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"TPS4654","DOI":"10.1200\/JCO.2020.38.15_suppl.TPS4654","article-title":"Multicenter phase II study of trastuzumab deruxtecan (DS-8201) for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial","volume":"38","author":"Ohba","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.cr.7290105","article-title":"MAPK signal pathways in the regulation of cell proliferation in mammalian cells","volume":"12","author":"Zhang","year":"2002","journal-title":"Cell Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/bjd.15829","article-title":"The evolving universe of BRAF mutations in melanoma","volume":"177","author":"Schaider","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/modpathol.2013.206","article-title":"BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma","volume":"27","author":"Goeppert","year":"2014","journal-title":"Mod. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1056\/NEJMoa1502309","article-title":"Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations","volume":"373","author":"Hyman","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1200\/JCO.2010.33.9473","article-title":"Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers","volume":"29","author":"Phelps","year":"2011","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ejca.2020.01.026","article-title":"Randomised phase II trial (SWOG S1310) of single agent MEK inhibitor trametinib Versus 5-fluorouracil or capecitabine in refractory advanced biliary cancer","volume":"130","author":"Kim","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s10637-018-0600-2","article-title":"Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer","volume":"36","author":"Finn","year":"2018","journal-title":"Investig. New Drugs"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41416-019-0523-5","article-title":"Enhanced antitumor effect of binimetinib in combination with capecitabine for biliary tract cancer patients with mutations in the RAS\/RAF\/MEK\/ERK pathway: Phase Ib study","volume":"121","author":"Kim","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1177\/1758834015616934","article-title":"Combination therapy with BRAF and MEK inhibitors for melanoma: Latest evidence and place in therapy","volume":"8","author":"Eroglu","year":"2016","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1200\/JCO.2019.37.4_suppl.187","article-title":"Efficacy and safety of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E\u2013mutated biliary tract cancer (BTC): A cohort of the ROAR basket trial","volume":"37","author":"Wainberg","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Subbiah, V., Lassen, U., \u00c9lez, E., Italiano, A., Curigliano, G., Javle, M., de Braud, F., Prager, G.W., Greil, R., and Stein, A. (2020). Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): A phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol.","DOI":"10.1016\/S1470-2045(20)30321-1"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1200\/JCO.2011.40.3774","article-title":"Targeting the hepatocyte growth factor-cMET axis in cancer therapy","volume":"30","author":"Blumenschein","year":"2012","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/bjc.2011.199","article-title":"Prognostic significance of overexpression of c-Met oncoprotein in cholangiocarcinoma","volume":"105","author":"Miyamoto","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1002\/cncr.30571","article-title":"A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma","volume":"123","author":"Goyal","year":"2017","journal-title":"Cancer"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1093\/annonc\/mdu157","article-title":"A phase I dose escalation study of oral c-MET inhibitor tivantinib (ARQ 197) in combination with gemcitabine in patients with solid tumors","volume":"25","author":"Pant","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ctrv.2018.11.001","article-title":"Targeting the PI3K\/AKT\/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives","volume":"72","author":"Corti","year":"2019","journal-title":"Cancer Treat Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13000-015-0381-2","article-title":"Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer","volume":"10","author":"Roa","year":"2015","journal-title":"Diagn. Pathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7698786","DOI":"10.1155\/2019\/7698786","article-title":"Contemporary Tailored Oncology Treatment of Biliary Tract Cancers","volume":"2019","author":"Turkes","year":"2019","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12935-015-0161-9","article-title":"Inhibition of the AKT pathway in cholangiocarcinoma by MK2206 reduces cellular viability via induction of apoptosis","volume":"15","author":"Wilson","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.21873\/anticanres.14282","article-title":"Second-line Treatment in Advanced Biliary Tract Cancer: Today and Tomorrow","volume":"40","author":"RIZZO","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Wu, C.-E., Chen, M.-H., and Yeh, C.-N. (2019). mTOR Inhibitors in Advanced Biliary Tract Cancers. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030500"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"12122","DOI":"10.1038\/srep12122","article-title":"Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer","volume":"5","author":"Ahn","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1093\/annonc\/mdu175","article-title":"Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: A phase II ITMO study","volume":"25","author":"Buzzoni","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_102","first-page":"71","article-title":"Cholangiocarcinoma pathogenesis: Role of the tumor microenvironment","volume":"1","author":"McMillin","year":"2012","journal-title":"Transl. Gastrointest. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Simone, V., Brunetti, O., Lupo, L., Testini, M., Maiorano, E., Simone, M., Longo, V., Rolfo, C., Peeters, M., and Scarpa, A. (2017). Targeting Angiogenesis in Biliary Tract Cancers: An Open Option. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020418"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/sj.bjc.6605458","article-title":"Sorafenib in patients with advanced biliary tract carcinoma: A phase II trial","volume":"102","author":"Bengala","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1200\/jco.2015.33.3_suppl.343","article-title":"Sunitinib as second-line treatment in patients with advanced intrahepatic cholangiocarcinoma (SUN-CK phase II trial): Safety, efficacy, and updated translational results","volume":"33","author":"Neuzillet","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ejca.2011.11.017","article-title":"A phase II study of sunitinib as a second-line treatment in advanced biliary tract carcinoma: A multicentre, multinational study","volume":"48","author":"Yi","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e16712","DOI":"10.1200\/JCO.2020.38.15_suppl.e16712","article-title":"A phase II study of anlotinib with cediranib as a second-line treatment for patients with advanced biliary tract cancers (aBTCs)","volume":"38","author":"Zhao","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/cncr.31872","article-title":"A phase 2 trial of regorafenib as a single agent in patients with chemotherapy-refractory, advanced, and metastatic biliary tract adenocarcinoma","volume":"125","author":"Sun","year":"2019","journal-title":"Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3464","DOI":"10.1002\/cncr.32964","article-title":"A multi-institutional phase 2 trial of regorafenib in refractory advanced biliary tract cancer","volume":"126","author":"Kim","year":"2020","journal-title":"Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.annonc.2020.05.018","article-title":"Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced\/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial","volume":"31","author":"Demols","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"v246","DOI":"10.1093\/annonc\/mdx369.106","article-title":"722P-A phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: Primary analysis results","volume":"28","author":"Ikeda","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e000023","DOI":"10.1136\/esmoopen-2015-000023","article-title":"NTRK gene fusions as novel targets of cancer therapy across multiple tumour types","volume":"1","author":"Amatu","year":"2016","journal-title":"Esmo Open"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41571-018-0113-0","article-title":"NTRK fusion-positive cancers and TRK inhibitor therapy","volume":"15","author":"Cocco","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1200\/JCO.2020.38.4_suppl.574","article-title":"NTRK gene fusions in biliary tract cancers","volume":"38","author":"Demols","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"viii23","DOI":"10.1093\/annonc\/mdz282","article-title":"TRK inhibitors in TRK fusion-positive cancers","volume":"30","author":"Drilon","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJMoa1714448","article-title":"Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children","volume":"378","author":"Drilon","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1470-2045(19)30691-6","article-title":"Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: Integrated analysis of three phase 1-2 trials","volume":"21","author":"Doebele","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1200\/JCO.2020.38.15_suppl.3605","article-title":"Efficacy and safety of entrectinib in patients (pts) with NTRK-fusion positive (NTRK-fp) solid tumors: An updated integrated analysis","volume":"38","author":"Rolfo","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.annonc.2020.04.056","article-title":"O-3 Efficacy and safety of entrectinib in NTRK fusion-positive gastrointestinal cancers: Updated integrated analysis of three clinical trials (STARTRK-2, STARTRK-1 and ALKA-372-001)","volume":"31","author":"Patel","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1093\/bib\/bbu046","article-title":"A selective review of robust variable selection with applications in bioinformatics","volume":"16","author":"Wu","year":"2015","journal-title":"Brief Bioinform."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Wu, C., Zhou, F., Ren, J., Li, X., Jiang, Y., and Ma, S. (2019). A Selective Review of Multi-Level Omics Data Integration Using Variable Selection. High-Throughput, 8.","DOI":"10.3390\/ht8010004"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"390","DOI":"10.21037\/jgo.2018.01.03","article-title":"Immune checkpoint inhibitors in gastrointestinal malignancies","volume":"9","author":"Jindal","year":"2018","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41568-019-0116-x","article-title":"The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy","volume":"19","author":"Havel","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"12348","DOI":"10.1038\/s41598-020-69366-4","article-title":"High PD-L1 expression is associated with therapeutic response to pembrolizumab in patients with advanced biliary tract cancer","volume":"10","author":"Ahn","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Marcus, L., Lemery, S.J., Keegan, P., and Pazdur, R. (2019). FDA Approval Summary: Pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin. Cancer Res.","DOI":"10.1158\/1078-0432.CCR-18-4070"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/annonc\/mdy495","article-title":"Development of tumor mutation burden as an immunotherapy biomarker: Utility for the oncology clinic","volume":"30","author":"Chan","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/JCO.19.02105","article-title":"Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability\/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study","volume":"38","author":"Marabelle","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1016\/S0959-8049(16)30326-4","article-title":"525 Safety and efficacy of pembrolizumab (MK-3475) in patients (pts) with advanced biliary tract cancer: Interim results of KEYNOTE-028","volume":"51","author":"Bang","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1200\/JCO.2019.37.15_suppl.4079","article-title":"Pembrolizumab (pembro) for advanced biliary adenocarcinoma: Results from the KEYNOTE-028 (KN028) and KEYNOTE-158 (KN158) basket studies","volume":"37","author":"Bang","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S2468-1253(19)30086-X","article-title":"Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer: A non-randomised, multicentre, open-label, phase 1 study","volume":"4","author":"Ueno","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1001\/jamaoncol.2020.0930","article-title":"A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer","volume":"6","author":"Kim","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Klein, O., Kee, D., Nagrial, A., Markman, B., Underhill, C., Michael, M., Jackett, L., Lum, C., Behren, A., and Palmer, J. (2020). Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients With Advanced Biliary Tract Cancers: Subgroup Analysis of a Phase 2 Nonrandomized Clinical Trial. JAMA Oncol., e202814.","DOI":"10.1001\/jamaoncol.2020.2814"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1158\/1078-0432.CCR-16-3215","article-title":"PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression","volume":"23","author":"Jiao","year":"2017","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1200\/JCO.2019.37.4_suppl.387","article-title":"Evaluation of safety and tolerability of durvalumab (D) with or without tremelimumab (T) in patients (pts) with biliary tract cancer (BTC)","volume":"37","author":"Ioka","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1200\/JCO.2020.38.4_suppl.547","article-title":"A pilot study of durvalumab\/tremelimumab (durva\/treme) and radiation (XRT) for metastatic biliary tract cancer (mBTC): Preliminary safety and efficacy","volume":"38","author":"Hong","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Ciciola, P., Cascetta, P., Bianco, C., Formisano, L., and Bianco, R. (2020). Combining Immune Checkpoint Inhibitors with Anti-Angiogenic Agents. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030675"},{"key":"ref_137","first-page":"1407","article-title":"Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open-Label, Phase I Trial (JVDF)","volume":"23","author":"Arkenau","year":"2018","journal-title":"Oncology"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1200\/JCO.2018.36.4_suppl.500","article-title":"Lenvatinib plus checkpoint inhibitors in patients (pts) with advanced intrahepatic cholangiocarcinoma (ICC): Preliminary data and correlation with next-generation sequencing","volume":"36","author":"Lin","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Yarchoan, M.C.L., Anders, R.A., Anne Noonan, A., Goff, L.W., Goyal, L., Lacy, J., Li, D., Patel, A., He, A.R., and Abou-Alfa, G. (2020, January 27\u201328). A multicenter randomized phase 2 trial of atezolizumab as monotherapy or in combination with cobimetinib in biliary tract cancers (BTCs): A NCI Experimental Therapeutics Clinical Trials Network (ETCTN) study. Proceedings of the 2020 American Association for Cancer Research Virtual Annual Meeting I, Philadelphia, PA, USA. Abstract CT043. bit.ly\/042BCTMCw.","DOI":"10.1158\/1538-7445.AM2020-CT043"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1089\/acm.2018.0125","article-title":"Integrative Treatment for Colorectal Cancer: A Comprehensive Approach","volume":"24","author":"Block","year":"2018","journal-title":"J. Altern Complement Med."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Jentzsch, V., Davis, J.A.A., and Djamgoz, M.B.A. (2020). Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management. Cancers, 12.","DOI":"10.3390\/cancers12113096"},{"key":"ref_142","first-page":"2369","article-title":"Effects of \u03c9-3 Fatty Acid Supplementation in Patients with Bile Duct or Pancreatic Cancer Undergoing Chemotherapy","volume":"38","author":"Abe","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.4161\/cc.9.15.12381","article-title":"Calcitriol enhances gemcitabine anti-tumor activity in vitro and in vivo by promoting apoptosis in a human pancreatic carcinoma model system","volume":"9","author":"Yu","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1002\/cncr.31676","article-title":"A phase 1, open-label, dose escalation study of intravenous paricalcitol in combination with gemcitabine in patients with advanced malignancies","volume":"124","author":"Fountzilas","year":"2018","journal-title":"Cancer"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/1\/97\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:10:45Z","timestamp":1760159445000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/1\/97"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,13]]},"references-count":144,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["biom11010097"],"URL":"https:\/\/doi.org\/10.3390\/biom11010097","relation":{},"ISSN":["2218-273X"],"issn-type":[{"type":"electronic","value":"2218-273X"}],"subject":[],"published":{"date-parts":[[2021,1,13]]}}}