Animal models of cholangiocarcinoma

Emilien Loeuillard, Samantha R. Fischbach, Gregory J. Gores, Sumera Rizvi

Research output: Contribution to journalReview article

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)982-992
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1865
Issue number5
DOIs
StatePublished - May 1 2019

Keywords

  • Orthotopic
  • Transduction
  • Transgenic
  • Xenotransplantation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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