Bile Duct Cancer: Treatment and Research – Latest Developments

Cholangiocarcinomas are a heterogeneous group of malignancies that can arise from any location along the biliary tree. They are anatomically classified as intrahepatic, perihilar, and distal cholangiocarcinomas. Intrahepatic cholangiocarcinoma, the less common type, arises proximal to the second-order bile ducts. Several risk factors eventually lead to either chronic inflammation and/or cholestasis, which lead to the development of cholangiocarcinomas. E-cadherin under increased influence of TGF-β transforms into N-cadherin and loses its cell adhesion property and starts invading, causing metastases. The surgical approach is aimed at curative intent by achieving R0 resection. The standard surgery is liver resection for proximal cholangiocarcinoma. After the radical surgical excision, the available modalities are chemotherapy and radiotherapy, or a combination of the two. Resistance to the activity of chemotherapy can be overcome by addition of Acelarin. Acelarin (NUC-1031) is a first-class nucleotide analog that presents a good safety profile and is under trial. Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of IDH1-mutant. However, there have been reported incidences of acquired ivosidenib resistance. Derazantinib is an oral drug. It is an ATP-competitive, pan-FGFR inhibitor with potent activity against FGFR1–3 kinases. Pembrolizumab is a humanized, highly specific monoclonal antibody against PD-1, which blocks the interaction between PD-1 and its ligands, PD-L1, and PD-L2. FDA approved it for DNA mismatch repair (MMR) deficiency and/or MSI-H, high grade solid tumors, including cholangiocarcinomas. Tumor vaccines are also under trial.