Establishment of an organoid bank of biliary tract and pancreatic cancers and its application for personalized therapy and future treatment.

Abstract

Biliary tract cancers and pancreatic cancers are aggressive malignancies that are difficult to diagnose early and have a poor prognosis. Patients with inoperable biliary tract and pancreatic cancers generally receive chemotherapy regimens including gemcitabine. However, the effects of these drugs are limited, and the 5-year survival rates of patients are very low. The newly developed three-dimensional culture system known as "organoid culture" allows long-term expansion of stem cells into cyst-like structures (organoids) with properties resembling those of the original tissues. We and other groups have successfully established long-term in vitro cultures of organoids derived from biliary tract and pancreatic cancers. Organoids derived from biliary tract and pancreatic cancers closely recapitulate the properties of the original tumors including genetic alterations, gene expression profiles, and histopathological structures. These patient-derived cancer organoids can be applied for drug sensitivity testing, drug screening, epigenetic therapy, and differentiation-inducing therapy to identify therapeutic agents optimal for each patient. We intend to further establish organoids derived from various cancer cases and construct an organoid bank of biliary tract and pancreatic cancers. These powerful in vitro preclinical models of refractory cancers may bridge the gap between basic research and clinical trials and allow personalized therapy for patients.