Evolution of the Experimental Models of Cholangiocarcinoma

Annamaria Massa, Chiara Varamo, Francesca Vita, Simona Tavolari, Caterina Peraldo-Neia, Giovanni Brandi, Alessandro Rizzo, Giuliana Cavalloni, Massimo Aglietta

Research output: Contribution to journalReview articlepeer-review

Abstract

Cholangiocarcinoma (CCA) is a rare, aggressive disease with poor overall survival. In advanced cases, surgery is often not possible or fails; in addition, there is a lack of effective and specific therapies. Multidisciplinary approaches and advanced technologies have improved the knowledge of CCA molecular pathogenesis, highlighting its extreme heterogeneity and high frequency of genetic and molecular aberrations. Effective preclinical models, therefore, should be based on a comparable level of complexity. In the past years, there has been a consistent increase in the number of available CCA models. The exploitation of even more complex CCA models is rising. Examples are the use of CRISPR/Cas9 or stabilized organoids for in vitro studies, as well as patient-derived xenografts or transgenic mouse models for in vivo applications. Here, we examine the available preclinical CCA models exploited to investigate: (i) carcinogenesis processes from initiation to progression; and (ii) tools for personalized therapy and innovative therapeutic approaches, including chemotherapy and immune/targeted therapies. For each model, we describe the potential applications, highlighting both its advantages and limits.

Original languageEnglish
JournalCancers
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 17 2020

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