Research Papers:

The effects of focal adhesion kinase and platelet-derived growth factor receptor beta inhibition in a patient-derived xenograft model of primary and metastatic Wilms tumor

Jamie M. Aye _, Laura L. Stafman, Adele P. Williams, Evan F. Garner, Jerry E. Stewart, Joshua C. Anderson, Smitha Mruthyunjayappa, Mary G. Waldrop, Caroline D. Goolsby, Hooper R. Markert, Colin Quinn, Raoud Marayati, Elizabeth Mroczek-Musulman, Christopher D. Willey, Karina J. Yoon, Kimberly F. Whelan and Elizabeth A. Beierle

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Oncotarget. 2019; 10:5534-5548. https://doi.org/10.18632/oncotarget.27165

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Jamie M. Aye1, Laura L. Stafman2, Adele P. Williams2, Evan F. Garner2, Jerry E. Stewart2, Joshua C. Anderson3, Smitha Mruthyunjayappa2, Mary G. Waldrop2, Caroline D. Goolsby2, Hooper R. Markert2, Colin Quinn2, Raoud Marayati2, Elizabeth Mroczek-Musulman4, Christopher D. Willey3, Karina J. Yoon5, Kimberly F. Whelan1 and Elizabeth A. Beierle2

1 Department of Pediatrics, Division of Hematology Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

2 Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

3 Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

4 Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

5 Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence to:

Jamie M. Aye,email: [email protected]

Keywords: kinase inhibition; Wilms tumor

Received: May 21, 2019     Accepted: August 12, 2019     Published: September 17, 2019


Aggressive therapies for patients with metastatic Wilms tumor (WT) with subsequent severe late effects warrant the search for novel therapies. The role of focal adhesion kinase (FAK), a non-receptor tyrosine kinase important in pediatric solid tumor development and progression, has not been examined in metastatic WT. Using a novel patient-derived xenograft (PDX) of a primary and matched, isogenic, metastatic WT, the hypothesis of the current study was that FAK would contribute to metastatic WT and small molecule inhibition would decrease tumor growth. Immunohistochemical staining, immunoblotting, cell viability and proliferation assays, cell cycle analysis, and cellular motility and attachment-independent growth assays were performed. FAK was present and phosphorylated in both WT PDXs and in the human samples from which they were derived. FAK inhibition decreased cellular survival, proliferation, and cell cycle progression in both PDXs but only significantly decreased migration, invasion, and attachment-independent growth in the primary WT PDX. Kinomic profiling revealed that platelet-derived growth factor receptor beta (PDGFRβ) may be affected by FAK inhibition in WT. Pharmacologic inhibition of FAK and PDGFRβ was synergistic in primary WT PDX cells. These findings broaden the knowledge of metastatic WT and support further investigations on the potential use of FAK and PDGFRβ inhibitors.

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