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Cell Reports Medicine

Cell Reports Medicine

IF: 11.7
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Modeling high-risk Wilms tumors enables the discovery of therapeutic vulnerability

Published:15 October 2024 DOI: 10.1016/j.xcrm.2024.101770 PMID: 39368485
Gui Ma,?Ang Gao,?Jiani Chen,?Peng Liu,?Rakesh Sarda,?Jessica Gulliver,?Yidan Wang,?Carstyn Joiner,?Mingshan Hu,?Eui-Jun Kim,?Herman Yeger,?Hau D Le,?Xiang Chen,?Wan-Ju Li,?Wei Xu

Abstract

Wilms tumor (WT) is the most common pediatric kidney cancer treated with standard chemotherapy. However, less-differentiated blastemal type of WT often relapses. To model the high-risk WT for therapeutic intervention, we introduce pluripotency factors into WiT49, a mixed-type WT cell line, to generate partially reprogrammed cells, namely WiT49-PRCs. When implanted into the kidney capsule in mice, WiT49-PRCs form kidney tumors and develop both liver and lung metastases, whereas WiT49 tumors do not metastasize. Histological characterization and gene expression signatures demonstrate that WiT49-PRCs recapitulate blastemal-predominant WTs. Moreover, drug screening in isogeneic WiT49 and WiT49-PRCs leads to the identification of epithelial- or blastemal-predominant WT-sensitive drugs, whose selectivity is validated in patient-derived xenografts (PDXs). Histone deacetylase (HDAC) inhibitors (e.g., panobinostat and romidepsin) are found universally effective across different WT and more potent than doxorubicin in PDXs. Taken together, WiT49-PRCs serve as a blastemal-predominant WT model for therapeutic intervention to treat patients with high-risk WT.

Substances (12)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 954 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 954 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 954 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 954 suppliers $15.00-$7060.00
Panobinostat 404950-80-7 C21H23N3O2 284 suppliers $10.00-$4735.50
Panobinostat 404950-80-7 C21H23N3O2 284 suppliers $10.00-$4735.50
Panobinostat 404950-80-7 C21H23N3O2 284 suppliers $10.00-$4735.50
Panobinostat 404950-80-7 C21H23N3O2 284 suppliers $10.00-$4735.50
Doxorubicin hydrochloride 25316-40-9 - Inquiry
Doxorubicin hydrochloride 25316-40-9 - Inquiry

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