REFERENCES
1. Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 2020;17:557-88.
2. Yamasaki S. Intrahepatic cholangiocarcinoma: macroscopic type and stage classification. J Hepatobiliary Pancreat Surg 2003;10:288-91.
4. Rodrigues PM, Olaizola P, Paiva NA, et al. Pathogenesis of cholangiocarcinoma. Annu Rev Pathol 2021;16:433-63.
5. Hucke F, Pinter M, Hucke M, et al. Changing epidemiological trends of hepatobiliary carcinomas in Austria 2010-2018. Cancers 2022;14:3093.
6. Turati F, Bertuccio P, Negri E, La Vecchia C. Epidemiology of cholangiocarcinoma. Hepatoma Res 2022;8:19.
7. Mauro E, Ferrer-Fàbrega J, Sauri T, et al. New challenges in the management of cholangiocarcinoma: the role of liver transplantation, locoregional therapies, and systemic therapy. Cancers 2023;15:1244.
8. Valle J, Wasan H, Palmer DH, et al. ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273-81.
9. Ohaegbulam KC, Koethe Y, Fung A, et al. The multidisciplinary management of cholangiocarcinoma. Cancer 2023;129:184-214.
10. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 2013;145:1215-29.
11. Nakamura H, Arai Y, Totoki Y, et al. Genomic spectra of biliary tract cancer. Nat Genet 2015;47:1003-10.
12. 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.
14. Lorenzini S, Bird TG, Boulter L, et al. Characterisation of a stereotypical cellular and extracellular adult liver progenitor cell niche in rodents and diseased human liver. Gut 2010;59:645-54.
15. Sirica AE, Gores GJ. Desmoplastic stroma and cholangiocarcinoma: clinical implications and therapeutic targeting. Hepatology 2014;59:2397-402.
16. Brivio S, Cadamuro M, Strazzabosco M, Fabris L. Tumor reactive stroma in cholangiocarcinoma: the fuel behind cancer aggressiveness. World J Hepatol 2017;9:455-68.
18. Muz B, de la Puente P, Azab F, Azab AK. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia 2015;3:83-92.
19. Morine Y, Shimada M, Utsunomiya T, et al. Hypoxia inducible factor expression in intrahepatic cholangiocarcinoma. Hepatogastroenterology 2011;58:1439-44.
20. Fabris L, Cadamuro M, Fiorotto R, et al. Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases. Hepatology 2006;43:1001-12.
21. Cadamuro M, Stecca T, Brivio S, et al. The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis 2018;1864:1435-43.
22. Akkoc Y, Peker N, Akcay A, Gozuacik D. Autophagy and Cancer Dormancy. Front Oncol 2021;11:627023.
23. Balayan V, Guddati AK. Tumor dormancy: biologic and therapeutic implications. World J Oncol 2022;13:8-19.
24. Baeriswyl V, Christofori G. The angiogenic switch in carcinogenesis. Semin Cancer Biol 2009;19:329-37.
27. Karakaş D, Cevatemre B, Ulukaya E. Cancer stem cells: emerging actors in both basic and clinical cancer research. Turk J Biol 2014;38:829-38.
28. Sirica AE. The role of cancer-associated myofibroblasts in intrahepatic cholangiocarcinoma. Nat Rev Gastroenterol Hepatol 2011;9:44-54.
29. Leyva-Illades D, McMillin M, Quinn M, Demorrow S. Cholangiocarcinoma pathogenesis: role of the tumor microenvironment. Transl Gastrointest Cancer 2012; 1:71-80.
30. Hasita H, Komohara Y, Okabe H, et al. Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma. Cancer Sci 2010;101:1913-9.
31. Jin MZ, Jin WL. The updated landscape of tumor microenvironment and drug repurposing. Signal Transduct Target Ther 2020;5:166.
32. Kawahara N, Ono M, Taguchi K, et al. Enhanced expression of thrombospondin-1 and hypovascularity in human cholangiocarcinoma. Hepatology 1998;28:1512-7.
33. Roy S, Glaser S, Chakraborty S. Inflammation and progression of cholangiocarcinoma: role of angiogenic and lymphangiogenic mechanisms. Front Med 2019;6:293.
34. 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;11:48-54.
35. Lubner SJ, Mahoney MR, Kolesar JL, 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;28:3491-7.
36. Guion-Dusserre JF, Lorgis V, Vincent J, Bengrine L, Ghiringhelli F. FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma. World J Gastroenterol 2015;21:2096-101.
37. Iyer RV, Pokuri VK, Groman A, et al. A multicenter phase II study of gemcitabine, capecitabine, and bevacizumab for locally advanced or metastatic biliary tract cancer. Am J Clin Oncol 2018;41:649-55.
38. Bréchon M, Dior M, Dréanic J, et al. Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers. Invest New Drugs 2018;36:156-62.
39. Larsen FO, Markussen A, Diness LV, Nielsen D. Efficacy and safety of capecitabine, irinotecan, gemcitabine, and bevacizumab as second-line treatment in advanced biliary tract cancer: a phase II study. Oncology 2018;94:19-24.
40. Pei SN, Liao CK, Chen YS, et al. A novel combination of bevacizumab with chemotherapy improves therapeutic effects for advanced biliary tract cancer: a retrospective, observational study. Cancers 2021;13:3831.
41. Bengala C, Bertolini F, Malavasi N, et al. Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial. Br J Cancer 2010;102:68-72.
42. Yi JH, Thongprasert S, Lee J, et al. A phase II study of sunitinib as a second-line treatment in advanced biliary tract carcinoma: a multicentre, multinational study. Eur J Cancer 2012;48:196-201.
43. El-Khoueiry AB, Rankin CJ, Ben-Josef E, et al. SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma. Invest New Drugs 2012;30:1646-51.
44. Lee JK, Capanu M, O'Reilly EM, et al. A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas. Br J Cancer 2013;109:915-9.
45. El-Khoueiry AB, Rankin C, Siegel AB, et al. S0941: a phase 2 SWOG study of sorafenib and erlotinib in patients with advanced gallbladder carcinoma or cholangiocarcinoma. Br J Cancer 2014;110:882-7.
46. Moehler M, Maderer A, Schimanski C, et al. Working Group of Internal Oncology. Gemcitabine plus sorafenib versus gemcitabine alone in advanced biliary tract cancer: a double-blind placebo-controlled multicentre phase II AIO study with biomarker and serum programme. Eur J Cancer 2014;50:3125-35.
47. Santoro A, Gebbia V, Pressiani T, et al. A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study. Ann Oncol 2015;26:542-7.
48. Valle JW, Wasan H, Lopes A, 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;16:967-78.
49. Dreyer C, Sablin MP, Bouattour M, et al. Disease control with sunitinib in advanced intrahepatic cholangiocarcinoma resistant to gemcitabine-oxaliplatin chemotherapy. World J Hepatol 2015;7:910-5.
50. Kessler ER, Eckhardt SG, Pitts TM, et al. Phase I trial of vandetanib in combination with gemcitabine and capecitabine in patients with advanced solid tumors with an expanded cohort in pancreatic and biliary cancers. Invest New Drugs 2016;34:176-83.
51. Shroff RT, Yarchoan M, O'Connor A, et al. The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma. Br J Cancer 2017;116:1402-7.
52. Sun W, Patel A, Normolle D, 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;125:902-9.
53. Kim RD, Sanoff HK, Poklepovic AS, et al. A multi-institutional phase 2 trial of regorafenib in refractory advanced biliary tract cancer. Cancer 2020;126:3464-70.
54. Cousin S, Cantarel C, Guegan JP, et al. Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. Eur J Cancer 2022;162:161-9.
55. Ding X, Li G, Sun W, et al. Sintilimab combined with lenvatinib for advanced intrahepatic cholangiocarcinoma in second-line setting-a multi-center observational study. Front Oncol 2022;12:907055.
56. Zhu C, Li H, Yang X, et al. Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study. Cancer Immunol Immunother 2023;72:2949-60.
57. Shi GM, Huang XY, Wu D, et al. Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study. Signal Transduct Target Ther 2023;8:106.
58. Holmes DI, Zachary I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol 2005;6:209.
60. Rajabi P, Neshat A, Mokhtari M, Rajabi MA, Eftekhari M, Tavakoli P. The role of VEGF in melanoma progression. J Res Med Sci 2012;17:534-9.
61. De Paola F, Granato AM, Scarpi E, et al. Vascular endothelial growth factor and prognosis in patients with node-negative breast cancer. Int J Cancer 2002;98:228-33.
62. Niklińska W, Burzykowski T, Chyczewski L, Nikliński J. Expression of vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC): association with p53 gene mutation and prognosis. Lung Cancer 2001;34 Suppl 2:S59-64.
63. Fabris L, Cadamuro M, Libbrecht L, et al. Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development. Hepatology 2008;47:719-28.
64. Mancino A, Mancino MG, Glaser SS, et al. Estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor. Dig Liver Dis 2009;41:156-63.
65. Hida Y, Morita T, Fujita M, et al. Vascular endothelial growth factor expression is an independent negative predictor in extrahepatic biliary tract carcinomas. Anticancer Res 1999;19:2257-60.
66. Möbius C, Demuth C, Aigner T, et al. Evaluation of VEGF a expression and microvascular density as prognostic factors in extrahepatic cholangiocarcinoma. Eur J Surg Oncol 2007;33:1025-9.
67. Yoshikawa D, Ojima H, Iwasaki M, et al. Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma. Br J Cancer 2008;98:418-25.
68. Cai C, Wang X, Fu Q, Chen A. The VEGF expression associated with prognosis in patients with intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. World J Surg Oncol 2022;20:40.
69. Calastri MCJ, Ferreira RF, Tenani GD, et al. Investigating VEGF. miR-145-3p, and miR-101-3p expression in patients with cholangiocarcinoma. Asian Pac J Cancer Prev 2022;23:2233-41.
70. Luo X, Jia W, Huang Z, et al. Effectiveness and safety of sorafenib in the treatment of unresectable and advanced intrahepatic cholangiocarcinoma: a pilot study. Oncotarget 2017;8:17246-57.
71. Huang MP, Gu SZ, Huang B, et al. Apatinib inhibits angiogenesis in intrahepatic cholangiocarcinoma by regulating the vascular endothelial growth factor receptor-2/signal transducer and activator of transcription factor 3/hypoxia inducible factor 1 subunit alpha signaling axis. Pharmacology 2021;106:509-19.
72. Peng H, Zhang Q, Li J, et al. Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma. Oncotarget 2016;7:17220-9.
73. Lin G, Wang B, Wu X, et al. Efficacy and safety of apatinib treatment for patients with advanced intrahepatic cholangiocarcinoma. Cancer Manag Res 2020;12:11523-6.
75. Zadeh G, Koushan K, Pillo L, Shannon P, Guha A. Role of ang1 and its interaction with VEGF-A in astrocytomas. J Neuropathol Exp Neurol 2004;63:978-89.
76. Moon WS, Rhyu KH, Kang MJ, et al. Overexpression of VEGF and angiopoietin 2: a key to high vascularity of hepatocellular carcinoma? Mod Pathol 2003;16:552-7.
77. Tang D, Nagano H, Yamamoto H, et al. Angiogenesis in cholangiocellular carcinoma: Expression of vascular endothelial growth factor, angiopoietin-1/2, thrombospondin-1 and clinicopathological significance. Oncol Rep 2006;15:525-32.
78. Voigtländer T, David S, Thamm K, et al. Angiopoietin-2 and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma. PLoS One 2014;9:e97046.
79. Kimawaha P, Jusakul A, Junsawang P, et al. Establishment of a potential serum biomarker panel for the diagnosis and prognosis of cholangiocarcinoma using decision tree algorithms. Diagnostics 2021;11:589.
80. Atanasov G, Hau HM, Dietel C, et al. Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma. J Surg Oncol 2016;114:91-8.
81. Atanasov G, Dietel C, Feldbrügge L, et al. Angiogenic miRNAs, the angiopoietin axis and related TIE2-expressing monocytes affect outcomes in cholangiocarcinoma. Oncotarget 2018;9:29921-33.
82. Adams JC. Thrombospondins: multifunctional regulators of cell interactions. Annu Rev Cell Dev Biol 2001;17:25-51.
83. Aishima S, Taguchi K, Sugimachi K, et al. The role of thymidine phosphorylase and thrombospondin-1 in angiogenesis and progression of intrahepatic cholangiocarcinoma. Int J Surg Pathol 2002;10:47-56.
84. Carpino G, Cardinale V, Di Giamberardino A, et al. Thrombospondin 1 and 2 along with PEDF inhibit angiogenesis and promote lymphangiogenesis in intrahepatic cholangiocarcinoma. J Hepatol 2021;75:1377-86.
85. Poon RT, Chung KK, Cheung ST, et al. Clinical significance of thrombospondin 1 expression in hepatocellular carcinoma. Clin Cancer Res 2004;10:4150-7.
86. Ding DY, Gan XJ, Zhang JN, et al. Serum thrombospondin-1 serves as a novel biomarker and agonist of gemcitabine-based chemotherapy in intrahepatic cholangiocarcinoma. Br J Cancer 2023;128:907-17.
88. Nelson J, Bagnato A, Battistini B, Nisen P. The endothelin axis: emerging role in cancer. Nat Rev Cancer 2003;3:110-6.
89. Eberl L, Bovey R, Juillerat-Jeanneret L. Endothelin-receptor antagonists are proapoptotic and antiproliferative in human colon cancer cells. Br J Cancer 2003;88:788-95.
90. Shen W, Xi H, Li C, et al. Endothelin-A receptor in gastric cancer and enhanced antitumor activity of trastuzumab in combination with the endothelin-A receptor antagonist ZD4054. Ann N Y Acad Sci 2019;1448:30-41.
91. Ahn HM, Kim DG, Kim YJ. Blockade of endothelin receptor A enhances the therapeutic efficacy of gemcitabine in pancreatic cancer cells. Biochem Biophys Res Commun 2020;527:568-73.
92. Rosanò L, Spinella F, Bagnato A. Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 2013;13:637-51.
93. Salani D, Di Castro V, Nicotra MR, et al. Role of endothelin-1 in neovascularization of ovarian carcinoma. Am J Pathol 2000;157:1537-47.
94. Fava G, Demorrow S, Gaudio E, et al. Endothelin inhibits cholangiocarcinoma growth by a decrease in the vascular endothelial growth factor expression. Liver Int 2009;29:1031-42.
