Immunotherapy and Targeted Agents for Biliary Tract Cancer

Dear Colleagues,

Biliary tract cancer (BTC) is the second most common primary liver tumor accounting for approximately 10-15% of all hepatobiliary malignancies and 3% of all gastrointestinal neoplasms. BTCs include a heterogeneous group of malignancies usually divided into intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of Vater cancer, according to anatomical location. Although traditionally considered rare tumors in Western countries, their incidence and mortality rate are on the whole rising worldwide. In particular, the incidence of intrahepatic cholangiocarcinoma is expected to further increase in the near future.

Currently, radical surgery with microscopically negative resection margins is the only potentially curative therapy available, although most patients are diagnosed in late disease stages (locally advanced/unresectable or metastatic). Moreover, even after complete surgical resection, the recurrence rate is high and the 5-year overall survival rate remains discouraging (20-35% at 5 years). As a result of the increasing availability of genomic sequencing data, many signaling pathways and new genetic aberrations involved in the carcinogenesis of BTC have recently been delineated and IDH1 mutations and FGFR2 fusions have been positioned as the two main driver alterations in intrahepatic cholangiocarcinoma and are being actively explored with specific antitargeted agents. However, many other alterations as NTRK rearrangements or BRAF mutations are also emerging as new potential targets in BTC. On the other hand, the role of immunotherapy in BTC is currently under investigation and checkpoint inhibitors are still looking for their niche in BTC. In this Special Issue, experts in this field will review the current immunotherapeutic and targeted approaches to the management of patients with the spectrum of BTC.

Prof. Dr. Massimo Aglietta
Prof. Dr. Giovanni Brandi
Guest Editors

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