Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.

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ID: 4226
2019
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Abstract
Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc, il2rga zebrafish that lacks adaptive and natural killer immune cells, can engraft a wide array of human cancers at 37°C, and permits the dynamic visualization of single engrafted cells. For example, photoconversion cell-lineage tracing identified migratory and proliferative cell states in human rhabdomyosarcoma, a pediatric cancer of muscle. Additional experiments identified the preclinical efficacy of combination olaparib PARP inhibitor and temozolomide DNA-damaging agent as an effective therapy for rhabdomyosarcoma and visualized therapeutic responses using a four-color FUCCI cell-cycle fluorescent reporter. These experiments identified that combination treatment arrested rhabdomyosarcoma cells in the G2 cell cycle prior to induction of apoptosis. Finally, patient-derived xenografts could be engrafted into our model, opening new avenues for developing personalized therapeutic approaches in the future.
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yan2019visualizingcell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Yan, Chuan;Brunson, Dalton C;Tang, Qin;Do, Daniel;Iftimia, Nicolae A;Moore, John C;Hayes, Madeline N;Welker, Alessandra M;Garcia, Elaine G;Dubash, Taronish D;Hong, Xin;Drapkin, Benjamin J;Myers, David T;Phat, Sarah;Volorio, Angela;Marvin, Dieuwke L;Ligorio, Matteo;Dershowitz, Lyle;McCarthy, Karin M;Karabacak, Murat N;Fletcher, Jonathan A;Sgroi, Dennis C;Iafrate, John A;Maheswaran, Shyamala;Dyson, Nick J;Haber, Daniel A;Rawls, John F;Langenau, David M;
Journal Cell
Year 2019
DOI
S0092-8674(19)30390-3
URL
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