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

Overview

MeSH Major

  • Cholangiocarcinoma
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy
  • Liver Neoplasms
  • Oncogene Proteins, Fusion

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.

publication date

  • November 26, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3845141

Digital Object Identifier (DOI)

  • 10.1073/pnas.1311707110

PubMed ID

  • 24154728

Additional Document Info

start page

  • 19513

end page

  • 8

volume

  • 110

number

  • 48