Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine
Jennifer L. Leiting, Stephen J. Murphy, John R. Bergquist, Matthew C. Hernandez, Tommy Ivanics, Amro M. Abdelrahman, Lin Yang, Isaac T. Lynch, James B. Smadbeck, Sean P. Cleary, David M. Nagorney, Michael Torbenson, Rondell P. Graham, Lewis R. Roberts, Gregory J. Gores, Rory L. Smoot, Mark J. Truty
Abstract
BACKGROUND & AIMS: Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Due to their low incidence, research into effective therapeutics has been limited. Novel research platforms for pre-clinical studies are desperately needed. We sought to develop a patient-derived biliary tract cancer xenograft catalog. METHODS: With appropriate consent and approval, surplus malignant tissues were obtained from surgical resection or radiographic biopsy and implanted into immunocompromised mice. Mice were monitored for xenograft growth. Established xenografts were verified by a hepatobiliary pathologist. Xenograft characteristics were correlated with original patient/tumor characteristics and oncologic outcomes. A subset of xenografts were then genomically characterized using Mate Pair sequencing (MPseq). RESULTS: . Sequencing also identified worse survival in patients with tumors containing tetraploid genomes. CONCLUSIONS: This is the largest series of biliary tract cancer xenografts reported to date. Histologic and genomic analysis of patient-derived xenografts demonstrates accurate recapitulation of original tumor morphology with direct correlations to patient outcomes. Successful development of biliary cancer tumografts is feasible and may be used to direct subsequent therapy in high recurrence risk patients. LAY SUMMARY: Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients.