1. Introduction – foreword
Welcome to the ‘Expert Opinion on Investigational Drugs’ special issue on biliary tract cancers (BTCs). BTCs are the second most common primary liver tumor; they are a heterogeneous group of malignancies that are typically divided according to their anatomical location. Intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer, and ampulla of Vater cancer are traditionally considered rare tumors in western countries; however, their incidence and mortality are rising globally.
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). However, 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 iCCA and are being actively explored with specific antitargeted agents. Other alterations such 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, international experts in this field examine key approaches under active investigation in clinical and preclinical research. They present critical analyses and integrate their own perspectives on promising drugs in clinical trials and the latest therapeutic strategies and drug targets. They illuminate the potential of precision medicine and offer supplementary strategic insights on how surgery and diagnostics can bolster the charge to tackle these difficult cancers.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose