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Role of Complement C3 in Kidney Cancer

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Grant Information

Project Title Role of Complement C3 in Kidney Cancer
Funding Opportunity Breakthrough Seed Funding
Funding Cycle Cycle 1
Award Date May 2023
Institution / Organization University of Washington
Principal Investigator(s) Christopher Blosser, MD; Shreeram Akilesh, MD, PhD
Lay Summary
BACKGROUND: Kidney cancer is one of the most common cancers in Washington, and has been increasing over the last 40 years. Clear cell renal cell carcinoma (ccRCC), the most common malignant kidney cancer, has multiple risk factors including hypertension, diabetes mellitus, black race, obesity and end-stage kidney disease. These risk factors are disproportionately prevalent in underserved communities across Washington State.
In preliminary studies, we have identified that complement C3, the central complement cascade protein, is increased in ccRCC patients and is associated with poor patient survival. We have also identified the mechanism controlling C3 upregulation in ccRCC. Yet, the role and impact of ccRCC-produced C3 is not well understood. To address this gap, our multidisciplinary team will target the following Specific Aims:
  • Aim 1. Establish if increased C3 gene and protein expression correlates with aggressive features of ccRCC tumors compared with normal tissue. Based on our insights into the mechanisms of C3 upregulation in ccRCC, we will test the efficacy of existing FDA-approved medications that target those mechanisms and determine if they suppress C3 levels and inhibit tumor growth.
  • Aim 2. Determine if circulating or tumor-produced C3 levels can be used as a prognostic biomarker for ccRCC and define whole transcriptome gene expression in ccRCC using digital spatial profiling technology.

IMPACT: This high-risk/high-impact project fulfills the goals of the Breakthrough Seed Funding program and will improve the lives of many Washington State citizens, including underserved communities. In conjunction with the matching DOD Idea Development Award ($675,000/3yrs, review February 2023) funding this project, the Breakthrough Seed Funding Grant will enable investigation of more patients’ samples to be analyzed with leading precision tools to produce the evidence to target the complement system, and result in a paradigm shift in kidney cancer treatment protocols.
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