# A New Strategy for Screening Effective Therapies for Metastatic Wilms Tumors

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $216,221

## Abstract

PROJECT SUMMARY
Wilms tumor (WT) is the second most common solid pediatric cancer that usually develops in young children
before age 5. WT encompass three main cell types: epithelium, stroma, and blasterma. WT are typically
treated with a combination of surgery, chemotherapy and radiotherapy. Although the survival rate for WT
patients is generally favorable, prognosis for patients with blastema dominant histology remain poor. Patients
with blastema dominant histology are more resistance to chemotherapy and have higher rate of cancer
recurrence, therefore there is unmet clinical need to improve therapy. The major obstacle for developing
novel therapies is the lack of cell lines and animal models representing high-risk blastemal WT. Because
blastemal WT represents aberrant ESCs, we reprogrammed WiT49 WT cells of epithelial origin into induced
pluripotent stem cells (iPSCs) and transplanted iPSCs into kidneys of mice. The tumors metastasized to the
liver and lung. Thus, WiT49-iPSCs represent the first blastemal WT model suitable for mechanistic studies to
understand the molecular changes distinguishing epithelial and blastemal types of WT and can be used to
screen FDA-approved drugs to find better treatments for children with aggressive WT. Because WiT49-iPSCs
acquire stem cell markers as well as metastatic traits as compared to WiT49, we hypothesize that WiT49-
iPSCs serve as a blastemal WT model suitable for mechanistic studies and drug screening to develop novel
therapies for metastatic blastemal WT. In this proposed study, we will (1) reprogram WiT49-iPSCs and
perform the teratoma assay to determine stem cell potency. (2) identify the epigenetic and chromatin
signatures distinguishing the blastemal and epithelial types of WT. (3) develop novel therapeutic strategies
for the treatment of WT. We will screen WiT49 and WiT49-iPSC cells against FDA-approved drugs and
epigenetic compounds to identify drugs effective against WiT49-iPSCs versus WiT-49 cells. Successful
completion of this project is expected to have a great impact on understanding the biology of kidney cancer
and establishing the invaluable experimental platform for the development of safer and more effective
therapies for Wilms tumors.

## Key facts

- **NIH application ID:** 10847688
- **Project number:** 1R21CA288336-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Wei Xu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $216,221
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847688

## Citation

> US National Institutes of Health, RePORTER application 10847688, A New Strategy for Screening Effective Therapies for Metastatic Wilms Tumors (1R21CA288336-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10847688. Licensed CC0.

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