Banales, J. M. et al. Cholangiocarcinoma: state-of-the-art knowledge and challenges. Liver Int. 39, 5–6 (2019).
Brindley, P. J. et al. Cholangiocarcinoma. Nat. Rev. Dis. Prim. 7, 65 (2021).
Banales, J. M. et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat. Rev. Gastroenterol. Hepatol. 17, 557–588 (2020).
Rizvi, S., Khan, S. A., Hallemeier, C. L., Kelley, R. K. & Gores, G. J. Cholangiocarcinoma– evolving concepts and therapeutic strategies. Nat. Rev. Clin. Oncol. 15, 95–111 (2018).
Affo, S. et al. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell 39, 883 (2021).
Yang, J. D. et al. DNA methylation markers for detection of cholangiocarcinoma: discovery, validation, and clinical testing in biliary brushings and plasma. Hepatol. Commun. 5, 1448–1459 (2021).
Zill, O. A. et al. Cell-free DNA next-generation sequencing in pancreatobiliary carcinomas. Cancer Discov. 5, 1040–1048 (2015).
Wu, M. J., Shi, L., Merritt, J., Zhu, A. X. & Bardeesy, N. Biology of IDH mutant cholangiocarcinoma. Hepatology 75, 1322–1337 (2022).
Kelley, R. K., Bridgewater, J., Gores, G. J. & Zhu, A. X. Systemic therapies for intrahepatic cholangiocarcinoma. J. Hepatol. 72, 353–363 (2020).
Abou-Alfa, G. K. et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 21, 671–684 (2020).
Javle, M. 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. 6, 803–815 (2021).
Goyal, L. et al. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N. Engl. J. Med. 388, 228–239 (2023).
US Food and Drug Administration. FDA grants accelerated approval to pemigatinib for cholangiocarcinoma with an FGFR2 rearrangement or fusion. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pemigatinib-cholangiocarcinoma-fgfr2-rearrangement-or-fusion (2020).
US Food and Drug Administration. FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma (2021).
US Food and Drug Administration. FDA grants accelerated approval to futibatinib for cholangiocarcinoma. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-futibatinib-cholangiocarcinoma (2022).
Abou-Alfa, G. K. et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 21, 796–807 (2020).
US Food and Drug Administration. FDA approves ivosidenib for advanced or metastatic cholangiocarcinoma. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-advanced-or-metastatic-cholangiocarcinoma (2022).
Gravely, A. K., Vibert, E. & Sapisochin, G. Surgical treatment of intrahepatic cholangiocarcinoma. J. Hepatol. https://doi.org/10.1016/j.jhep.2022.01.004 (2022).
Wang, J., Loeuillard, E., Gores, G. J. & Ilyas, S. I. Cholangiocarcinoma: what are the most valuable therapeutic targets – cancer-associated fibroblasts, immune cells, or beyond T cells? Expert. Opin. Ther. Targets 25, 835–845 (2021).
Loeuillard, E. et al. Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma. J. Clin. Invest. 130, 5380–5396 (2020).
Ruffolo, L. I. et al. GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity. Gut 71, 1386–1398 (2022).
Zhang, Q. et al. Gut microbiome directs hepatocytes to recruit MDSCs and promote cholangiocarcinoma. Cancer Discov. 11, 1248–1267 (2021).
Gani, F. et al. Program death 1 immune checkpoint and tumor microenvironment: implications for patients with intrahepatic cholangiocarcinoma. Ann. Surg. Oncol. 23, 2610–2617 (2016).
Zhou, G. et al. Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules. J. Hepatol. 71, 753–762 (2019).
Ghidini, M. et al. Characterisation of the immune-related transcriptome in resected biliary tract cancers. Eur. J. Cancer 86, 158–165 (2017).
Ma, L. et al. Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell 36, 418–430.e6 (2019).
Fabris, L., Sato, K., Alpini, G. & Strazzabosco, M. The tumor microenvironment in cholangiocarcinoma progression. Hepatology 73, 75–85 (2021).
Piha-Paul, S. A. et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: results from the KEYNOTE-158 and KEYNOTE-028 studies. Int. J. Cancer 147, 2190–2198 (2020).
Buettner, S. et al. The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma. Surgery 164, 411–418 (2018).
Peng, D. et al. Lymphocyte to monocyte ratio predicts resectability and early recurrence of Bismuth-Corlette type IV hilar cholangiocarcinoma. J. Gastrointest. Surg. 24, 330–340 (2020).
Tsilimigras, D. I. et al. The systemic immune-inflammation index predicts prognosis in intrahepatic cholangiocarcinoma: an international multi-institutional analysis. HPB 22, 1667–1674 (2020).
Sun, D. et al. CD86+/CD206+ tumor-associated macrophages predict prognosis of patients with intrahepatic cholangiocarcinoma. PeerJ 8, e8458 (2020).
Yuan, D. et al. Kupffer cell-derived TNF triggers cholangiocellular tumorigenesis through JNK due to chronic mitochondrial dysfunction and ROS. Cancer Cell 31, 771–789.e6 (2017).
Boulter, L. et al. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J. Clin. Invest. 125, 1269–1285 (2015).
Dwyer, B. J. et al. TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression. J. Hepatol. 74, 860–872 (2021).
Veglia, F., Perego, M. & Gabrilovich, D. Myeloid-derived suppressor cells coming of age. Nat. Immunol. 19, 108–119 (2018).
Xu, X. D. et al. Circulating myeloid-derived suppressor cells in patients with pancreatic cancer. Hepatobiliary Pancreat. Dis. Int. 15, 99–105 (2016).
Meyer, C. et al. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol. Immunother. 63, 247–257 (2014).
Song, G. et al. Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma. Nat. Commun. 13, 1642 (2022).
Bao, X. et al. Molecular subgroups of intrahepatic cholangiocarcinoma discovered by single-cell RNA sequencing-assisted multiomics analysis. Cancer Immunol. Res. 10, 811–828 (2022).
Keenan, B. P. et al. Circulating monocytes associated with anti-PD-1 resistance in human biliary cancer induce T cell paralysis. Cell Rep. 40, 111384 (2022).
Tavazoie, M. F. et al. LXR/ApoE activation restricts innate immune suppression in cancer. Cell 172, 825–840.e18 (2018).
Vonderheide, R. H. CD40 agonist antibodies in cancer immunotherapy. Annu. Rev. Med. 71, 47–58 (2020).
Diggs, L. P. et al. CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma. J. Hepatol. 74, 1145–1154 (2021).
Wabitsch, S. et al. Anti-PD-1 in combination with trametinib suppresses tumor growth and improves survival of intrahepatic cholangiocarcinoma in mice. Cell Mol. Gastroenterol. Hepatol. 12, 1166–1178 (2021).
Affo, S., Yu, L. X. & Schwabe, R. F. The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu. Rev. Pathol. 12, 153–186 (2017).
Brivio, S., Cadamuro, M., Strazzabosco, M. & Fabris, L. Tumor reactive stroma in cholangiocarcinoma: the fuel behind cancer aggressiveness. World J. Hepatol. 9, 455–468 (2017).
Sirica, A. E., Campbell, D. J. & Dumur, C. I. Cancer-associated fibroblasts in intrahepatic cholangiocarcinoma. Curr. Opin. Gastroenterol. 27, 276–284 (2011).
Sirica, A. E. & Gores, G. J. Desmoplastic stroma and cholangiocarcinoma: clinical implications and therapeutic targeting. Hepatology 59, 2397–2402 (2014).
Fabris, L. et al. The tumour microenvironment and immune milieu of cholangiocarcinoma. Liver Int. 39, 63–78 (2019).
Mertens, J. C. et al. Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma. Cancer Res. 73, 897–907 (2013).
Chen, Y., McAndrews, K. M. & Kalluri, R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat. Rev. Clin. Oncol. 18, 792–804 (2021).
Campbell, D. J., Dumur, C. I., Lamour, N. F., Dewitt, J. L. & Sirica, A. E. Novel organotypic culture model of cholangiocarcinoma progression. Hepatol. Res. 42, 1119–1130 (2012).
Biffi, G. & Tuveson, D. A. Diversity and biology of cancer-associated fibroblasts. Physiol. Rev. 101, 147–176 (2021).
Kalluri, R. The biology and function of fibroblasts in cancer. Nat. Rev. Cancer 16, 582–598 (2016).
Bhattacharjee, S. et al. Tumor restriction by type I collagen opposes tumor-promoting effects of cancer-associated fibroblasts. J. Clin. Invest. https://doi.org/10.1172/JCI146987 (2021).
Martin-Serrano, M. A. et al. Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications. Gut https://doi.org/10.1136/gutjnl-2021-326514 (2022).
Zhang, M. et al. Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma. J. Hepatol. 73, 1118–1130 (2020).
Ravichandra, A., Bhattacharjee, S. & Affo, S. Cancer-associated fibroblasts in intrahepatic cholangiocarcinoma progression and therapeutic resistance. Adv. Cancer Res. 156, 201–226 (2022).
Chen, Y. et al. Type I collagen deletion in αSMA+ myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer. Cancer Cell 39, 548–565.e6 (2021).
Liu, M. C. et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann. Oncol. 31, 745–759 (2020).
Cohen, J. D. et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359, 926–930 (2018).
Wasenang, W., Chaiyarit, P., Proungvitaya, S. & Limpaiboon, T. Serum cell-free DNA methylation of OPCML and HOXD9 as a biomarker that may aid in differential diagnosis between cholangiocarcinoma and other biliary diseases. Clin. Epigenetics 11, 39 (2019).
Ettrich, T. J. et al. Genotyping of circulating tumor DNA in cholangiocarcinoma reveals diagnostic and prognostic information. Sci. Rep. 9, 13261 (2019).
Mody, K. et al. Circulating tumor DNA profiling of advanced biliary tract cancers. JCO Precis. Oncol. 3, 1–9 (2019).
Moreno Luna, L. E. et al. Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology 131, 1064–1072 (2006).
Barr Fritcher, E. G. et al. An optimized set of fluorescence in situ hybridization probes for detection of pancreatobiliary tract cancer in cytology brush samples. Gastroenterology 149, 1813–1824.e1 (2015).
Gonda, T. A. et al. Mutation profile and fluorescence in situ hybridization analyses increase detection of malignancies in biliary strictures. Clin. Gastroenterol. Hepatol. 15, 913–919.e1 (2017).
Singhi, A. D. et al. Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures. Gut 69, 52–61 (2020).
Arechederra, M. et al. Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures. Gut 71, 1141–1151 (2022).
Andresen, K. et al. Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma. Hepatology 61, 1651–1659 (2015).
Loi, E. et al. HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples. Br. J. Cancer 126, 1783–1794 (2022).
Shigehara, K. et al. Real-time PCR-based analysis of the human bile microRNAome identifies miR-9 as a potential diagnostic biomarker for biliary tract cancer. PLoS ONE 6, e23584 (2011).
Han, H. S. et al. Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p as potential biomarkers for cholangiocarcinoma. Hepatobiliary Pancreat. Dis. Int. 19, 41–50 (2020).
Berchuck, J. E. et al. The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer. Ann. Oncol. 33, 1269–1283 (2022).
Andersen, J. B. et al. Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors. Gastroenterology 142, 1021–1031.e15 (2012).
Montal, R. et al. Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma. J. Hepatol. 73, 315–327 (2020).
Sia, D. et al. Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes. Gastroenterology 144, 829–840 (2013).
Job, S. et al. Identification of four immune subtypes characterized by distinct composition and functions of tumor microenvironment in intrahepatic cholangiocarcinoma. Hepatology 72, 965–981 (2020).
Lowery, M. A. et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin. Cancer Res. 24, 4154–4161 (2018).
Weinberg, B. A. et al. Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets. J. Gastrointest. Oncol. 10, 652–662 (2019).
Wardell, C. P. et al. Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations. J. Hepatol. 68, 959–969 (2018).
Jusakul, A. et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov. 7, 1116–1135 (2017).
Nakamura, H. et al. Genomic spectra of biliary tract cancer. Nat. Genet. 47, 1003–1010 (2015).
Boscoe, A. N., Rolland, C. & Kelley, R. K. Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: a systematic literature review. J. Gastrointest. Oncol. 10, 751–765 (2019).
Chaisaingmongkol, J. et al. Common molecular subtypes among Asian hepatocellular carcinoma and cholangiocarcinoma. Cancer Cell 32, 57–70.e3 (2017).
Chan-On, W. et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat. Genet. 45, 1474–1478 (2013).
Bekaii-Saab, T. S., Bridgewater, J. & Normanno, N. Practical considerations in screening for genetic alterations in cholangiocarcinoma. Ann. Oncol. 32, 1111–1126 (2021).
Lamarca, A. et al. Molecular profiling in daily clinical practice: practicalities in advanced cholangiocarcinoma and other biliary tract cancers. J. Clin. Med. https://doi.org/10.3390/jcm9092854 (2020).
National Comprehensive Cancer Network. NCCN guidelines: hepatobiliary cancer. NCCN https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1438 (2022).
Haugsten, E. M., Wiedlocha, A., Olsnes, S. & Wesche, J. Roles of fibroblast growth factor receptors in carcinogenesis. Mol. Cancer Res. 8, 1439–1452 (2010).
Babina, I. S. & Turner, N. C. Advances and challenges in targeting FGFR signalling in cancer. Nat. Rev. Cancer 17, 318–332 (2017).
Wu, Y. M. et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 3, 636–647 (2013).
Graham, R. P. et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum. Pathol. 45, 1630–1638 (2014).
Arai, Y. et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology 59, 1427–1434 (2014).
Becker, Z. BridgeBio says it’s undeterred after Truseltiq partner withdraws application, discontinues drug. FIERCE Pharma https://www.fiercepharma.com/pharma/bridgebios-cancer-drug-truseltiqs-future-unclear-partner-helsinn-withdrawing-nda (2022).
Droz Dit Busset, M. et al. Derazantinib for patients with intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements: primary results from the phase II study FIDES-01 [abstract 47P]. Ann. Oncol. 32 (Suppl. 5), S376 (2021).
Krook, M. A. et al. Efficacy of FGFR inhibitors and combination therapies for acquired resistance in FGFR2-fusion cholangiocarcinoma. Mol. Cancer Ther. 19, 847–857 (2020).
Krook, M. A. et al. Tumor heterogeneity and acquired drug resistance in FGFR2-fusion-positive cholangiocarcinoma through rapid research autopsy. Cold Spring Harb. Mol. Case Stud. https://doi.org/10.1101/mcs.a004002 (2019).
Goyal, L. et al. Polyclonal secondary FGFR2 mutations drive acquired resistance to FGFR inhibition in patients with FGFR2 fusion-positive cholangiocarcinoma. Cancer Discov. 7, 252–263 (2017).
Goyal, L. et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma. Cancer Discov. 9, 1064–1079 (2019).
Sootome, H. et al. Futibatinib is a novel irreversible FGFR 1-4 inhibitor that shows selective antitumor activity against FGFR-deregulated tumors. Cancer Res. 80, 4986–4997 (2020).
Meric-Bernstam, F. et al. Futibatinib, an irreversible FGFR1-4 inhibitor, in patients with advanced solid tumors harboring FGF/FGFR aberrations: a phase I dose-expansion study. Cancer Discov. 12, 402–415 (2022).
Casaletto, J. et al. RLY-4008, a novel precision therapy for FGFR2-driven cancers designed to potently and selectively inhibit FGFR2 and FGFR2 resistance mutations [abstract]. Cancer Res. 81 (Suppl. 13), 1455 (2021).
Franovic, A. et al. Activity of KIN-3248, a next-generation pan-FGFR inhibitor, against acquired FGFR-gatekeeper and molecular-brake drug resistance mutations [abstract]. J. Clin. Oncol. 40 (Suppl. 4), 461 (2022).
Goyal, L. et al. First results of RLY-4008, a potent and highly selective FGFR2 inhibitor in a first-in-human study in patients with FGFR2-altered cholangiocarcinoma and multiple solid tumors [abstract]. Mol. Cancer Ther. 20 (Suppl. 12), P02-02 (2021).
Lu, C. & Thompson, C. B. Metabolic regulation of epigenetics. Cell Metab. 16, 9–17 (2012).
Inoue, S. et al. Mutant IDH1 downregulates ATM and alters DNA repair and sensitivity to DNA damage independent of TET2. Cancer Cell 30, 337–348 (2016).
Sulkowski, P. L. et al. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.aal2463 (2017).
Valle, J. W., Lamarca, A., Goyal, L., Barriuso, J. & Zhu, A. X. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 7, 943–962 (2017).
Subbiah, V. 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. 21, 1234–1243 (2020).
US Food and Drug Administration. FDA grants accelerated approval of dabrafenib in combination with trametinib for unresectable or metastatic solid tumors with BRAF V600E mutation. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dabrafenib-combination-trametinib-unresectable-or-metastatic-solid (2022).
Subbiah, V. et al. Pan-cancer efficacy of vemurafenib in BRAFV600-mutant non-melanoma cancers. Cancer Discov. 10, 657–663 (2020).
Galdy, S. et al. HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target? Cancer Metastasis Rev. 36, 141–157 (2017).
Javle, M. et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 22, 1290–1300 (2021).
Ohba, A. 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) [abstract]. J. Clin. Oncol. 40 (Suppl. 16), 4006 (2022).
Lee, C. K. et al. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19-14). Lancet Gastroenterol. Hepatol. https://doi.org/10.1016/S2468-1253(22)00335-1 (2022).
Harding, J. J. et al. Targeting HER2 mutation-positive advanced biliary tract cancers with neratinib: final results from the phase 2 SUMMIT basket trial. J. Clin. Oncol. 40, 4079–4079 (2022).
Meric-Bernstam, F. et al. Zanidatamab (ZW25) in HER2-positive biliary tract cancers (BTCs): results from a phase I study [abstract]. J. Clin. Oncol. 39 (Suppl. 3), 299 (2021).
Westphalen, C. B. et al. Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population. NPJ Precis. Oncol. 5, 69 (2021).
Drilon, A. et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N. Engl. J. Med. 378, 731–739 (2018).
US Food and Drug Administration. FDA approves larotrectinib for solid tumors with NTRK gene fusions. FDA https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0 (2018).
Doebele, R. C. et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 21, 271–282 (2020).
US Food and Drug Administration. FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinib-ntrk-solid-tumors-and-ros-1-nsclc (2019).
Parimi, V. et al. Genomic landscape of 891 RET fusions detected across diverse solid tumor types. NPJ Precis. Oncol. 7, 10 (2023).
Subbiah, V. et al. Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nat. Med. 28, 1640–1645 (2022).
Subbiah, V. 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. 23, 1261–1273 (2022).
Valle, J. W., Kelley, R. K., Nervi, B., Oh, D. Y. & Zhu, A. X. Biliary tract cancer. Lancet 397, 428–444 (2021).
Lamarca, A., Edeline, J. & Goyal, L. How I treat biliary tract cancer. ESMO Open 7, 100378 (2022).
Le, D. T. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357, 409–413 (2017).
Maio, M. et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase 2 KEYNOTE-158 study. Ann. Oncol. https://doi.org/10.1016/j.annonc.2022.05.519 (2022).
US Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication (2017).
US Food and Drug Administration. FDA approves pembrolizumab for adults and children with TMB-H solid tumors. FDA https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors (2020).
Marabelle, A. et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 21, 1353–1365 (2020).
Ma, K. et al. PD-L1 and PD-1 expression correlate with prognosis in extrahepatic cholangiocarcinoma. Oncol. Lett. 14, 250–256 (2017).
Zhu, Y. et al. Programmed death ligand 1 expression in human intrahepatic cholangiocarcinoma and its association with prognosis and CD8+ T-cell immune responses. Cancer Manag. Res. 10, 4113–4123 (2018).
Fluxa, P. et al. High CD8+ and absence of Foxp3+ T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival. BMC Cancer 18, 243 (2018).
Goeppert, B. et al. Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer. Br. J. Cancer 113, 1343–1349 (2015).
Sun, D. et al. Anti-PD-1 therapy combined with chemotherapy in patients with advanced biliary tract cancer. Cancer Immunol. Immunother. 68, 1527–1535 (2019).
Sahai, V. et al. A multicenter randomized phase II study of nivolumab in combination with gemcitabine/cisplatin or ipilimumab as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-01) [abstract]. J. Clin. Oncol. 38 (Suppl. 15), 4582 (2020).
Liu, T. et al. Toripalimab with chemotherapy as first-line treatment for advanced biliary tract tumors: a preliminary analysis of safety and efficacy of an open-label phase II clinical study [abstract 53P]. Ann. Oncol. 31 (Suppl. 4), S261 (2020).
Oh, D. Y. et al. Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Lancet Gastroenterol. Hepatol. 7, 522–532 (2022).
Oh, D.-Y. et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. https://doi.org/10.1056/EVIDoa2200015 (2022).
Burris, H. A. et al. Patient-reported outcomes for the phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer [abstract]. J. Clin. Oncol. 40 (Suppl. 16), 4070 (2022).
He, A. et al. Outcomes by primary tumour location in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study [abstract O-1]. Ann. Oncol. 33 (Suppl. 4), S378 (2022).
Okusaka, T. et al. Outcomes by disease status in patients with advanced biliary tract cancer treated wtih durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study [abstract 93P]. Ann. Oncol. 33 (Suppl. 9), S1471 (2022).
Vogel, A. et al. Regional subgroup analysis of the phase 3 TOPAZ-1 study of durvalumab (D) plus gemcitabine and cisplatin (GC) in advanced biliary tract cancer (BTC) [abstract]. J. Clin. Oncol. 40 (Suppl. 16), 4075 (2022).
US Food and Drug Administration. FDA D.I.S.C.O. burst edition: FDA approval of Imfinzi (durvalumab) for adult patients with locally advanced or metastatic biliary tract cancer. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval-imfinzi-durvalumab-adult-patients-locally-advanced-or (2022).
Kelley, R. K. et al. 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 https://doi.org/10.1016/S0140-6736(23)00727-4 (2023).
Villaneuva, L. et al. Lenvatinib plus pembrolizumab for patients with previously treated biliary tract cancers in the multicohort phase II LEAP-005 study [abstract]. J. Clin. Oncol. 39 (Suppl. 3), 321 (2021).
Sapisochin, G. et al. Transplant oncology in primary and metastatic liver tumors: principles, evidence, and opportunities. Ann. Surg. 273, 483–493 (2021).
McMillan, R. R. et al. Survival following liver transplantation for locally advanced, unresectable intrahepatic cholangiocarcinoma. Am. J. Transpl. 22, 823–832 (2022).
Ivanics, T., Toso, C., Ilyas, S. I. & Sapisochin, G. Transplant oncology in locally advanced intrahepatic cholangiocarcinoma: one more step on a long road. Am. J. Transpl. 22, 685–686 (2022).
Jain, A. et al. Cholangiocarcinoma with FGFR genetic aberrations: a unique clinical phenotype. JCO Precis. Oncol. 2, 1–12 (2018).
Franssen, S. et al. Comparison of hepatic arterial infusion pump chemotherapy vs resection for patients with multifocal intrahepatic cholangiocarcinoma. JAMA Surg. https://doi.org/10.1001/jamasurg.2022.1298 (2022).
Sapisochin, G. et al. “Very early” intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients? Am. J. Transpl. 14, 660–667 (2014).
Sapisochin, G. et al. Liver transplantation for “very early” intrahepatic cholangiocarcinoma: international retrospective study supporting a prospective assessment. Hepatology 64, 1178–1188 (2016).
Jung, D. H. et al. Clinicopathological features and prognosis of intrahepatic cholangiocarcinoma after liver transplantation and resection. Ann. Transpl. 22, 42–52 (2017).
De Martin, E. et al. Analysis of liver resection versus liver transplantation on outcome of small intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma in the setting of cirrhosis. Liver Transpl. 26, 785–798 (2020).
Lunsford, K. E. et al. Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. Lancet Gastroenterol. Hepatol. 3, 337–348 (2018).
Ito, T. et al. A 3-decade, single-center experience of liver transplantation for cholangiocarcinoma: impact of era, tumor size, location, and neoadjuvant therapy. Liver Transpl. 28, 386–396 (2022).