Patient-Derived Xenograft Case Study

Developing Xenograft Lines to Identify Therapeutic Vulnerabilities in Bladder Cancer

Scientists don’t yet know whether the process of mRNA translation represents a therapeutic vulnerability in bladder cancer. The lab of Dr. Andrew Hsieh at Fred Hutchinson Cancer Research Center sought to investigate this question using patient-derived xenograft, or PDX, models derived from bladder cancer patients.
 

The Challenge

The Hsieh Lab was eager to begin their project but had no experience in developing PDX lines.
 

The Approach

The team purchased six models from the Jackson Laboratory and acquired lines developed at the University of Washington, and they sought the help of the Preclinical Modeling Core Lab’s PDX program to develop them. With the help of PDX program lead Elizabeth Cromwell, Hsieh’s team was able to resurrect the models they purchased and acquired, passage them, validate them and subsequently use them for preclinical trials. Throughout the project, Cromwell provided Hsieh Lab members with invaluable instruction on the intricacies of working with PDX models.

Organoid
The Hsieh Lab team developed organoid lines from different PDX models of bladder cancer the lab created in collaboration with the PMCL's PDX program. Dr. Sujata Jana, Hsieh Lab
Immunohistochemistry (IHC) staining showing differential expression of a specific protein in different PDX models created by the Preclinical Modeling Core Lab's PDX program in collaboration with the Hsieh Lab.
Immunohistochemistry staining showing differential expression of a specific protein in different PDX models created by the PMCL's PDX program in collaboration with the Hsieh Lab. Dr. Sujata Jana, Hsieh Lab

The Outcome

Out of the multiple lines the Hsieh Lab purchased and acquired, all except one were successfully reconstituted. Cromwell provided hands-on assistance, helping Hsieh’s team to troubleshoot the unsuccessful line and working with JAX to investigate potential additional methods to bring the line back.

Thanks to their work with the PDX models, Hsieh’s team was able to answer their research question. They learned that specific genetic backgrounds of bladder cancer are more sensitive to translation inhibitors. And their findings kicked off several mechanistic studies that are still underway. Hsieh’s team plans to publish this work in a high-impact journal, and they’ve used their findings to apply for new National Institutes of Health funding.
 

Read More

Learn more about the Hsieh Lab’s research.

“Elizabeth is extremely diligent and responsive to all questions we had. She will also work with you to tailor your experiment to your needs. Overall, an excellent experience.”

– Dr. Andrew Hsieh, Associate Professor, Human Biology and Clinical Research divisions, Fred Hutch