REFERENCES
2. Endo I, Gonen M, Yopp AC, et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg 2008;248:84-96.
3. Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: an overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin 2023;73:198-222.
4. Bekaii-saab T, Bridgewater J, Normanno N. Practical considerations in screening for genetic alterations in cholangiocarcinoma. Ann Oncol 2021;32:1111-26.
5. Lamarca A, Barriuso J, McNamara MG, Valle JW. Molecular targeted therapies: ready for "prime time" in biliary tract cancer. J Hepatol 2020;73:170-85.
7. Goyal L, Meric-Bernstam F, Hollebecque A, et al. FOENIX-CCA2 Study Investigators. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med 2023;388:228-39.
8. Kendre G, Murugesan K, Brummer T, Segatto O, Saborowski A, Vogel A. Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma. J Hepatol 2023;78:614-26.
9. Verdaguer H, Saurí T, Acosta DA, et al. ESMO scale for clinical actionability of molecular targets driving targeted treatment in patients with cholangiocarcinoma. Clin Cancer Res 2022;28:1662-71.
10. Wang XY, Zhu WW, Wang Z, et al. Driver mutations of intrahepatic cholangiocarcinoma shape clinically relevant genomic clusters with distinct molecular features and therapeutic vulnerabilities. Theranostics 2022;12:260-76.
11. Carapeto F, Bozorgui B, Shroff RT, et al. The immunogenomic landscape of resected intrahepatic cholangiocarcinoma. Hepatology 2022;75:297-308.
12. Cleary JM, Raghavan S, Wu Q, et al. FGFR2 extracellular domain in-frame deletions are therapeutically targetable genomic alterations that function as oncogenic drivers in cholangiocarcinoma. Cancer Discov 2021;11:2488-505.
13. Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res 2018;24:4154-61.
14. Jusakul A, Cutcutache I, Yong CH, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov 2017;7:1116-35.
15. Verlingue L, Hollebecque A, Boige V, Ducreux M, Malka D, Ferté C. Matching genomic molecular aberrations with molecular targeted agents: are biliary tract cancers an ideal playground? Eur J Cancer 2017;81:161-73.
16. Weinberg BA, Xiu J, Lindberg MR, et al. Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets. J Gastrointest Oncol 2019;10:652-62.
17. Zhang Y, Ma Z, Li C, et al. The genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers. Nat Commun 2022;13:3061.
18. Komuta M. Intrahepatic cholangiocarcinoma: tumour heterogeneity and its clinical relevance. Clin Mol Hepatol 2022;28:396-407.
19. Song G, Shi Y, Meng L, et al. Publisher correction: single-cell transcriptomic analysis suggests two molecularly distinct subtypes of intrahepatic cholangiocarcinoma. Nat Commun 2022;13:2848.
20. Dong L, Lu D, Chen R, et al. Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma. Cancer Cell 2022;40:70-87.e15.
21. Dentro SC, Leshchiner I, Haase K, et al. PCAWG Evolution and Heterogeneity Working Group and the PCAWG Consortium. Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell 2021;184:2239-54.e39.
22. Lin Y, Peng L, Dong L, et al. Geospatial immune heterogeneity reflects the diverse tumor-immune interactions in intrahepatic cholangiocarcinoma. Cancer Discov 2022;12:2350-71.
23. Xiang X, Liu Z, Zhang C, et al. IDH mutation subgroup status associates with intratumor heterogeneity and the tumor microenvironment in intrahepatic cholangiocarcinoma. Adv Sci 2021;8:e2101230.
24. Lin J, Dai Y, Sang C, et al. Multimodule characterization of immune subgroups in intrahepatic cholangiocarcinoma reveals distinct therapeutic vulnerabilities. J Immunother Cancer 2022;10:e004892.
25. Farrell B, Breeze AL. Structure, activation and dysregulation of fibroblast growth factor receptor kinases: perspectives for clinical targeting. Biochem Soc Trans 2018;46:1753-70.
26. Wiedemann M, Trueb B. Characterization of a novel protein (FGFRL1) from human cartilage related to FGF receptors. Genomics 2000;69:275-9.
27. Helsten T, Elkin S, Arthur E, Tomson BN, Carter J, Kurzrock R. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res 2016;22:259-67.
28. 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;21:671-84.
29. Shi GM, Huang XY, Wen TF, et al. Pemigatinib in previously treated Chinese patients with locally advanced or metastatic cholangiocarcinoma carrying FGFR2 fusions or rearrangements: a phase II study. Cancer Med 2023;12:4137-46.
30. NCCN. NCCN Guidelines. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1517 [Last accessed on 14 Nov 2023].
31. Javle M, Roychowdhury S, Kelley RK, et al. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol 2021;6:803-15.
32. Borad M, Javle M, Shaib W, et al. 59P efficacy of derazantinib in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions, mutations or amplifications. Ann Oncol 2022;33:S567-8.
33. Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010;17:225-34.
34. Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009;462:739-44.
35. Bleeker FE, Atai NA, Lamba S, et al. The prognostic IDH1(R132) mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma. Acta Neuropathol 2010;119:487-94.
36. Pirozzi CJ, Yan H. The implications of IDH mutations for cancer development and therapy. Nat Rev Clin Oncol 2021;18:645-61.
37. Yang Z, Jiang B, Wang Y, et al. 2-HG inhibits necroptosis by stimulating DNMT1-dependent hypermethylation of the RIP3 promoter. Cell Rep 2017;19:1846-57.
38. Fujiwara H, Tateishi K, Misumi K, et al. Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation. Sci Rep 2019;9:18859.
39. Wu MJ, Shi L, Dubrot J, et al. Mutant IDH Inhibits IFNγ-TET2 signaling to promote immunoevasion and tumor maintenance in cholangiocarcinoma. Cancer Discov 2022;12:812-35.
40. Chen X, Yang P, Qiao Y, et al. Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2. Sci Rep 2022;12:18830.
41. Wintheiser G, Zemla T, Shi Q, et al. Isocitrate dehydrogenase-mutated cholangiocarcinoma: natural history and clinical outcomes. JCO Precis Oncol 2022;6:e2100156.
42. Wang J, Zhang ZG, Ding ZY, et al. IDH1 mutation correlates with a beneficial prognosis and suppresses tumor growth in IHCC. J Surg Res 2018;231:116-25.
43. 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;45:1470-3.
44. 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;32:3091-100.
45. Goyal L, Govindan A, Sheth RA, et al. Prognosis and clinicopathologic features of patients with advanced stage isocitrate dehydrogenase (IDH) mutant and IDH wild-type intrahepatic cholangiocarcinoma. Oncologist 2015;20:1019-27.
46. Jolissaint JS, Soares KC, Seier KP, et al. Intrahepatic cholangiocarcinoma with lymph node metastasis: treatment-related outcomes and the role of tumor genomics in patient selection. Clin Cancer Res 2021;27:4101-8.
47. Niger M, Nichetti F, Casadei-Gardini A, et al. Platinum sensitivity in patients with IDH1/2 mutated vs wild-type intrahepatic cholangiocarcinoma: a propensity score-based study. Int J Cancer 2022;151:1310-20.
48. 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;21:796-807.
49. Levantini E, Maroni G, Del Re M, Tenen DG. EGFR signaling pathway as therapeutic target in human cancers. Semin Cancer Biol 2022;85:253-75.
50. Hsu JL, Hung MC. The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer. Cancer Metastasis Rev 2016;35:575-88.
51. Kumagai S, Koyama S, Nishikawa H. Antitumour immunity regulated by aberrant ERBB family signalling. Nat Rev Cancer 2021;21:181-97.
52. Treekitkarnmongkol W, Suthiphongchai T. High expression of ErbB2 contributes to cholangiocarcinoma cell invasion and proliferation through AKT/p70S6K. World J Gastroenterol 2010;16:4047-54.
53. Swain SM, Shastry M, Hamilton E. Targeting HER2-positive breast cancer: advances and future directions. Nat Rev Drug Discov 2023;22:101-26.
54. Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol 2021;22:1290-300.
55. Ohba A, Morizane C, Kawamoto Y, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing unresectable or recurrent biliary tract cancer (BTC): An investigator-initiated multicenter phase 2 study (HERB trial). JCO 2022;40:4006.
56. Harding JJ, Piha-Paul SA, Shah RH, et al. Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers. Nat Commun 2023;14:630.
57. Meric-Bernstam F, Beeram M, Hamilton E, et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Lancet Oncol 2022;23:1558-70.
58. Sithanandam G, Druck T, Cannizzaro LA, Leuzzi G, Huebner K, Rapp UR. B-raf and a B-raf pseudogene are located on 7q in man. Oncogene 1992;7:795-9.
59. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54.
60. Robertson S, Hyder O, Dodson R, et al. The frequency of KRAS and BRAF mutations in intrahepatic cholangiocarcinomas and their correlation with clinical outcome. Hum Pathol 2013;44:2768-73.
61. Iversen L, Tu HL, Lin WC, et al. Molecular kinetics. Ras activation by SOS: allosteric regulation by altered fluctuation dynamics. Science 2014;345:50-4.
62. Huang L, Guo Z, Wang F, Fu L. KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther 2021;6:386.
63. Zhu C, Guan X, Zhang X, et al. Targeting KRAS mutant cancers: from druggable therapy to drug resistance. Mol Cancer 2022;21:159.
64. Parikh K, Banna G, Liu SV, et al. Drugging KRAS: current perspectives and state-of-art review. J Hematol Oncol 2022;15:152.
65. 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;21:1234-43.
66. Salama AKS, Li S, Macrae ER, et al. Dabrafenib and trametinib in patients with tumors with BRAFV600E mutations: results of the NCI-MATCH trial subprotocol H. J Clin Oncol 2020;38:3895-904.
67. Subbiah V, Puzanov I, Blay JY, et al. Pan-cancer efficacy of vemurafenib in BRAFV600-mutant non-melanoma cancers. Cancer Discov 2020;10:657-63.
68. Kim JW, Lee KH, Kim JW, et al. 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. Br J Cancer 2019;121:332-9.
69. Subbiah V, Cassier PA, Siena S, et al. Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nat Med 2022;28:1640-5.
70. Subbiah V, Wolf J, Konda B, et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Lancet Oncol 2022;23:1261-73.
71. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018;15:731-47.
72. Yoshino T, Pentheroudakis G, Mishima S, et al. JSCO-ESMO-ASCO-JSMO-TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions. Ann Oncol 2020;31:861-72.
73. Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov 2015;5:25-34.
75. Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020;21:531-40.
76. Demetri GD, De Braud F, Drilon A, et al. Updated integrated analysis of the efficacy and safety of entrectinib in patients with NTRK fusion-positive solid tumors. Clin Cancer Res 2022;28:1302-12.
77. Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res 2019;25:3753-8.
79. Jung J, Heo YJ, Park S. High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis. J Immunother Cancer 2023;11:e006454.
80. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409-13.
81. Borghaei H, Ciuleanu TE, Lee JS, et al. Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Ann Oncol 2023;34:173-85.
82. Maio M, Ascierto PA, Manzyuk L, et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Ann Oncol 2022;33:929-38.
83. Andre T, Berton D, Curigliano G, et al. Safety and efficacy of anti-PD-1 antibody dostarlimab in patients (pts) with mismatch repair-deficient (dMMR) solid cancers: results from GARNET study. JCO 2021;39:9.
84. Schenker M, Burotto M, Richardet M, et al. Abstract CT022: checkMate 848: a randomized, open-label, phase 2 study of nivolumab in combination with ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden. Cancer Res 2022;82:CT022.
85. 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;6:888-94.
86. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid 2022;1:EVIDoa2200015.
87. Kelley RK, Ueno M, Yoo C, et al. KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023;401:1853-65.
88. Mosele F, Remon J, Mateo J, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO precision medicine working group. Ann Oncol 2020;31:1491-505.
89. Marchiò C, Scaltriti M, Ladanyi M, et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 2019;30:1417-27.
90. Graham RP, Barr Fritcher EG, Pestova E, et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol 2014;45:1630-8.
91. Rompianesi G, Di Martino M, Gordon-Weeks A, Montalti R, Troisi R. Liquid biopsy in cholangiocarcinoma: Current status and future perspectives. World J Gastrointest Oncol 2021;13:332-50.
92. Berchuck JE, Facchinetti F, DiToro DF, et al. The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer. Ann Oncol 2022;33:1269-83.
93. 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;9:1064-79.
94. 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;80:4986-97.
95. Calvert AE, Chalastanis A, Wu Y, et al. Cancer-associated IDH1 promotes growth and resistance to targeted therapies in the absence of mutation. Cell Rep 2017;19:1858-73.
96. Intlekofer AM, Shih AH, Wang B, et al. Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations. Nature 2018;559:125-9.
97. Harding JJ, Lowery MA, Shih AH, et al. Isoform switching as a mechanism of acquired resistance to mutant isocitrate dehydrogenase inhibition. Cancer Discov 2018;8:1540-7.
98. Lito P, Rosen N, Solit DB. Tumor adaptation and resistance to RAF inhibitors. Nat Med 2013;19:1401-9.
99. 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;120:165-71.
100. 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;25:4888-97.
101. Kim SB, Meric-Bernstam F, Kalyan A, et al. First-in-human phase I study of aprutumab ixadotin, a fibroblast growth factor receptor 2 antibody-drug conjugate (BAY 1187982) in patients with advanced cancer. Target Oncol 2019;14:591-601.
102. Ahn DH, Uson Junior PLS, Masci P, et al. A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma. Invest New Drugs 2022;40:134-41.