Bissig-Choisat B, Kettlun-Leyton C, Legras XL, Zorman B, Barzi M, Chen LL, Amin MD, Huang YH, Pautler RG, Hampton OA, Prakash MM, Muzny D, Doddapaneni H, Hu J, Shi Y, Gaber WM, Hicks MJ, Thompson PA, Lu Y, Mills GB, Finegold M, Goss JA, Parsons DW, Vasudevan SA, Sumazin P, Lopez-Terrada D, Bissig KD
Metastatic patient-derived xenograft model and isogenic cell lines for pediatric liver cancer research. J Hepatol. 2016 April 65(2):325-33.
Pediatric liver cancer is a rare but serious disease that is poorly understood; no experimental animal model has been able to replicate the behavior and molecular mechanisms driving these tumors.
In this paper, we developed a new orthotopic technique that enabled us to graft a series of patient-derived tumor cells into mice, from all major subtypes of pediatric liver cancer: hepatoblastoma, hepatocellular cancer, and hepatocellular malignant neoplasm.
We also developed stem cell culturing techniques to derive new pediatric cancer cell lines from the xenografted mice.
This study demonstrated that the patient-derived tumor xenografts recapitulate the histological, genetic, biological, and behavioral characteristics of the primary tumors.
We tested a therapy for an aggressive hepatocellular malignant neoplasm with the MEK1 inhibitor trametinib and the IPI3 kinase inhibitor NVP-BKM120, which strongly inhibited tumor growth.
This model is thus a valuable tool for studying tumor biology and patient-specific therapeutic responses.