Abstract
The prognosis of patients with solid tumours has remarkably improved with the development of molecular-targeted drugs and immune checkpoint inhibitors. However, the improvements in the prognosis of pancreatic cancer and biliary tract cancer is delayed compared to other carcinomas, and the 5-year survival rates of distal-stage disease are approximately 10 and 20%, respectively. However, a comprehensive analysis of tumour cells using The Cancer Genome Atlas (TCGA) project has led to the identification of various driver mutations. Evidently, few mutations exist across organs, and basket trials targeting driver mutations regardless of the primary organ are being actively conducted. Such basket trials not only focus on the gate keeper-type oncogene mutations, such as HER2 and BRAF, but also focus on the caretaker-type tumour suppressor genes, such as BRCA1/2, mismatch repair-related genes, which cause hereditary cancer syndrome. As oncogene panel testing is a vital approach in routine practice, clinicians should devise a strategy for improved understanding of the cancer genome. Here, the gene mutation profiles of pancreatic cancer and biliary tract cancer have been outlined and the current status of tumour-agnostic therapy in these cancers has been reported.
Highlights
Pancreatic cancer and biliary tract cancer are malignant tumours with the worst prognosis
Site-specific gene abnormalities of EGFR, ERBB3, phosphatase, and tensin homolog (PTEN), ARID2, mixed-lineage leukaemia protein 2 (MLL2), MLL3, telomerase reverse transcriptase (TERT) promoter mutations were found in gallbladder cancer, PRKACA or PRKACB fusion, ELF3, ARID1B in extrahepatic bile duct cancer, and FGFR2 fusion, isocitrate dehydrogenase 1/2 (IDH1/2), EPHA2, and BRCA1 associated protein-1 (BAP1) in intrahepatic bile duct cancer
Since abnormalities in the homologous recombination deficiency (HRD)-related genes are observed in pancreatic cancer, clinical trials to verify the efficacy of the poly (ADPribose) polymerase (PARP) inhibitors have been conducted in pancreatic cancer patients with germline mutations in BRCA1/2 [45,46,47,48]
Summary
Pancreatic cancer and biliary tract cancer are malignant tumours with the worst prognosis. FOLFIRINOX [2] or combination therapy with gemcitabine and nab-paclitaxel [3] is the first-line therapy for unresectable or metastatic pancreatic cancer, and gemcitabine and CDDP (cisplatin) for biliary tract cancer [4]. These treatments are not based on gene mutation profiles, and the median overall survival is less than one year with either treatment. The cancer panel test introduced in clinical practice has led to the identification of druggable mutations in approximately 10% of the pancreatic cancers and 40% of the biliary tract cancers [15]. We review the genome profiles of pancreatic cancers and biliary tract cancers and the approaches used for the development of drugs for the indicated actionable mutations
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