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Remarkable advancements in techniques of genomic profiling and bioinformatics have led to the accumulation of vast amounts of knowledge on the genomic profiles of biliary tract cancer (BTC). Recent largescale molecular profiling studies have not only highlighted genomic differences characterizing tumors of the intrahepatic and extrahepatic bile ducts and gallbladder, but have also revealed differences in genomic profiles pertaining to associated risk factors. Novel genomic alterations such as FGFR2 fusions and IDH1/2 mutations in intrahepatic cholangiocarcinoma (ICC) and ERBB2 alterations in gallbladder cancer (GBCA) are emerging as targeted therapy options capable of advancing precision medicine for the care of these patients. Moreover, variable genomic alterations also appear to impact prognosis and overall disease outcome independent from their therapy selection value. High mutational burden and increased expression of immune checkpoint-related proteins observed in a subset of BTC also show a potential for guidance of immunotherapy. Thus, comprehensive genomic profiling (CGP) is rapidly achieving status as an integral component of precision medicine and is starting to become invaluable in guiding the management of patients with BTC, a rare disease with dismal outcome.

The potential role of comprehensive genomic profiling to guide targeted therapy for patients with biliary cancer