Animal models of cholangiocarcinoma

Biochim Biophys Acta Mol Basis Dis. 2019 May 1;1865(5):982-992. doi: 10.1016/j.bbadis.2018.03.026. Epub 2018 Apr 5.

Abstract

Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy with a poor overall prognosis. There is a critical need to develop effective targeted therapies for the treatment of this lethal disease. In an effort to address this challenge, preclinical in vivo studies have become paramount in understanding CCA carcinogenesis, progression, and therapy. Various CCA animal models exist including carcinogen-based models in which animals develop CCA after exposure to a carcinogen, genetically engineered mouse models in which genetic changes are induced in mice leading to CCA, murine syngeneic orthotopic models, as well as xenograft tumors derived from xenotransplantation of CCA cells, organoids, and patient-derived tissue. Each type has distinct advantages as well as shortcomings. In the ideal animal model of CCA, the tumor arises from the biliary tract in an immunocompetent host with a species-matched tumor microenvironment. Such a model would also be time-efficient, recapitulate the genetic and histopathological features of human CCA, and predict therapeutic response in humans. Recently developed biliary tract transduction and orthotopic syngeneic transplant mouse models encompass several of these elements. Herein, we review the different animal models of CCA, their advantages and deficiencies, as well as features which mimic human CCA.

Keywords: Orthotopic; Transduction; Transgenic; Xenotransplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bile Duct Neoplasms / etiology*
  • Bile Duct Neoplasms / pathology
  • Cholangiocarcinoma / etiology*
  • Cholangiocarcinoma / pathology
  • Cholestasis / complications
  • Disease Models, Animal*
  • Gene Editing / methods
  • Humans
  • Xenograft Model Antitumor Assays / methods