Precision Medicine of Hepatobiliary and Pancreatic Cancers: Focusing on Clinical Trial Outcomes

SIMPLE SUMMARY: Recently, tumor-agnostic precision medicine employing comprehensive genome profiling (CGP) and using next-generation sequencing (NGS) has been progressing. This review focuses on the recent progress in precision medicine for advanced unresectable hepatobiliary and pancreatic cancers. We highlight therapies that target several regulators of cancer cell growth and tumor-agnostic therapies that effectively treat biliary and pancreatic cancers. We also discuss our current understanding of precision medicine methods developed using NGS of circulating tumor DNA (ctDNA) as a liquid biopsy technique. ABSTRACT: Tumor-agnostic precision medicine employing comprehensive genome profiling (CGP) and using next-generation sequencing (NGS) has been progressing recently. This review focuses on precision medicine for advanced unresectable hepatobiliary and pancreatic cancers. In this paper, for biliary tract cancer (BTC), therapies that target several regulators of cancer cell growth, including isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2) fusion, proto-oncogene B-Raf (BRAF), and human epidermal growth factor receptor 2 (HER2) alterations, are reviewed. For pancreatic ductal adenocarcinoma (PDAC), therapies for Kirsten rat sarcoma virus (KRAS) gene mutation G12C, neuregulin (NRG)1, and breast cancer type 1 and 2 susceptibility (BRCA1/2), gene alterations are summarized. On the other hand, precision medicine targets were not established for hepatocellular carcinoma (HCC), although telomerase reverse transcriptase (TERT), tumor protein P53 (TP53), and Wnt/β catenin signaling alterations have been recognized as HCC driver oncogenes. Tumor-agnostic therapies for microsatellite instability-high (MSI-H) and neurotropic tyrosine receptor kinase (NTRK) fusion cancers effectively treat biliary and pancreatic cancers. Precision medicine methods developed using NGS of circulating tumor DNA (ctDNA) and utilizing a liquid biopsy technique are discussed.