Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer

Beatrice Bissig-Choisat, Claudia Kettlun-Leyton, Xavier D. Legras, Barry Zorman, Mercedes Barzi, Leon L. Chen, Mansi D. Amin, Yung Hsin Huang, Robia G. Pautler, Oliver A. Hampton, Masand M. Prakash, Diane Yang, Malgorzata Borowiak, Donna Muzny, Harsha Vardhan Doddapaneni, Jianhong Hu, Yan Shi, M. Waleed Gaber, M. John Hicks, Patrick A. ThompsonYiling Lu, Gordon B. Mills, Milton Finegold, John A. Goss, D. Williams Parsons, Sanjeev A. Vasudevan, Pavel Sumazin, Dolores López-Terrada, Karl Dimiter Bissig

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Background & Aims Pediatric liver cancer is a rare but serious disease whose incidence is rising, and for which the therapeutic options are limited. Development of more targeted, less toxic therapies is hindered by the lack of an experimental animal model that captures the heterogeneity and metastatic capability of these tumors. Methods Here we established an orthotopic engraftment technique to model a series of patient-derived tumor xenograft (PDTX) from pediatric liver cancers of all major histologic subtypes: hepatoblastoma, hepatocellular cancer and hepatocellular malignant neoplasm. We utilized standard (immuno) staining methods for histological characterization, RNA sequencing for gene expression profiling and genome sequencing for identification of druggable targets. We also adapted stem cell culturing techniques to derive two new pediatric cancer cell lines from the xenografted mice. Results The patient-derived tumor xenografts recapitulated the histologic, genetic, and biological characteristics—including the metastatic behavior—of the corresponding primary tumors. Furthermore, the gene expression profiles of the two new liver cancer cell lines closely resemble those of the primary tumors. Targeted therapy of PDTX from an aggressive hepatocellular malignant neoplasm with the MEK1 inhibitor trametinib and pan-class I PI3 kinase inhibitor NVP-BKM120 resulted in significant growth inhibition, thus confirming this PDTX model as a valuable tool to study tumor biology and patient-specific therapeutic responses. Conclusions The novel metastatic xenograft model and the isogenic xenograft-derived cell lines described in this study provide reliable tools for developing mutation- and patient-specific therapies for pediatric liver cancer. Lay summary Pediatric liver cancer is a rare but serious disease and no experimental animal model currently captures the complexity and metastatic capability of these tumors. We have established a novel animal model using human tumor tissue that recapitulates the genetic and biological characteristics of this cancer. We demonstrate that our patient-derived animal model, as well as two new cell lines, are useful tools for experimental therapies.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalJournal of Hepatology
Issue number2
StatePublished - Aug 1 2016


  • Patient-derived xenograft
  • Pediatric liver cancer
  • Therapeutic testing

ASJC Scopus subject areas

  • Hepatology


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