Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target

Anna Saborowski, Michael Saborowski, Monika A. Davare, Brian J. Druker, David S. Klimstra, Scott W. Lowe

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Cholangiocarcinoma is the second most common primary liver cancer and responds poorly to existing therapies. Intrahepatic cholangiocarcinoma (ICC) likely originates from the biliary tree and develops within the hepatic parenchyma. We have generated a flexible orthotopic allograft mouse model of ICC that incorporates common genetic alterations identified in human ICC and histologically resembles the human disease. We examined the utility of this model to validate driver alterations in ICC and tested their suitability as therapeutic targets. Specifically, we showed that the fused-in-glioblastoma-c- ros-oncogene1 (FIG-ROS1(S); FIG- ROS) fusion gene dramatically accelerates ICC development and that its inactivation in established tumors has a potent antitumor effect. Our studies establish a versatile model of ICC that will be a useful preclinical tool and validate ROS1 fusions as potent oncoproteins and therapeutic targets in ICC and potentially other tumor types.

Original languageEnglish (US)
Pages (from-to)19513-19518
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number48
DOIs
StatePublished - Nov 26 2013

ASJC Scopus subject areas

  • General

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