Panelists discuss how comprehensive next-generation sequencing is performed to identify key biomarkers including IDH1/2 mutations and FGFR2 fusions (predominantly in intrahepatic cholangiocarcinoma), HER2 amplifications (common in gallbladder cancers), and other actionable alterations like BRAF V600E mutations, with NCCN guidelines recommending testing for specific biomarkers to guide targeted therapy decisions and clinical trial enrollment given the rarity of biliary tract cancers and limited treatment options.