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Review

Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options

1
Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (Milan), Italy
2
Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele (Milan), Italy
3
Internal Medicine Center, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (Milan), Italy
4
Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London W120HS, UK
5
Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK
6
Department of Medical Oncology, “Euromedica” General Clinic, 54645 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
These authors contributed equally to the manuscript.
These authors contributed equally to the manuscript.
Cancers 2020, 12(11), 3370; https://doi.org/10.3390/cancers12113370
Received: 15 October 2020 / Revised: 8 November 2020 / Accepted: 11 November 2020 / Published: 13 November 2020
Incidence of biliary tract cancer is increasing, and patients are frequently diagnosed with unresectable or metastatic disease, when therapeutic options are limited. Due to these reasons, prognosis remains poor and new systemic treatment options are urgently needed. This article reviews the new available data on molecular heterogeneity of biliary tract cancer and especially intrahepatic cholangiocarcinoma and the novel therapeutic strategies offered by the improved knowledge of the biology of this disease. For these reasons, this topic is of relevant interest for the oncology and hepatology community.
Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC. View Full-Text
Keywords: biliary tract cancer; cholangiocarcinoma; molecular characterization; tumor heterogeneity; FGFR; IDH; targeted agents biliary tract cancer; cholangiocarcinoma; molecular characterization; tumor heterogeneity; FGFR; IDH; targeted agents
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MDPI and ACS Style

Personeni, N.; Lleo, A.; Pressiani, T.; Colapietro, F.; Openshaw, M.R.; Stavraka, C.; Pouptsis, A.; Pinato, D.J.; Rimassa, L. Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options. Cancers 2020, 12, 3370. https://doi.org/10.3390/cancers12113370

AMA Style

Personeni N, Lleo A, Pressiani T, Colapietro F, Openshaw MR, Stavraka C, Pouptsis A, Pinato DJ, Rimassa L. Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options. Cancers. 2020; 12(11):3370. https://doi.org/10.3390/cancers12113370

Chicago/Turabian Style

Personeni, Nicola, Ana Lleo, Tiziana Pressiani, Francesca Colapietro, Mark R. Openshaw, Chara Stavraka, Athanasios Pouptsis, David J. Pinato, and Lorenza Rimassa. 2020. "Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options" Cancers 12, no. 11: 3370. https://doi.org/10.3390/cancers12113370

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