The Importance of Molecular Testing in the Treatment of Cholangiocarcinoma

Abstract

Cholangiocarcinomas (CCA) are uncommon malignant tumours and are classified as intrahepatic, perihilar, or distal, depending on where they arise within the biliary epithelium. Surgery is still the only curative treatment, yet diagnosis is often made too late for this to be a viable option. For patients with locally advanced (unresectable), metastatic, or recurrent CCA, guidelines recommend palliative first-line chemotherapy with platinum compounds plus gemcitabine. However, the benefits are limited, with median overall survival being below 1 year, and there is an urgent need for novel, more effective treatment options. Next-generation sequencing has revealed information about the genetic makeup of the CCA subtypes and CCA, especially intrahepatic, rank among tumours with the highest rate of potentially actionable gene alterations. A number of next-generation sequencing platforms are now commercially available, opening up the possibility for routine molecular testing at the time of diagnosis to allow a more personalised, targeted treatment approach. However, despite the availability of these platforms, barriers to their use remain, including issues with reimbursement in some countries. Several clinical trials have been completed or are underway in CCA, investigating treatments directed against potentially actionable targets, such as FGFR2, IDH, NTRK, BRAF, and HER2. Some of these treatments are showing promising efficacy. Alongside, or before, initiating standard chemotherapy, efforts should be made to identify specific targets in all patients via molecular testing and treat eligible patients accordingly or enrol them in appropriate clinical trials.

Keywords

• biliary tract cancer
• cholangiocarcinoma (cca)
• driver mutations
• next-generation sequencing
• targeted therapy