Establishment of Working Models of Papillary Kidney Cancer by Transformation of the Proximal Nephron
Abstract
Rationale: Limited treatment options exist for patients with advanced forms of papillary renal cell carcinoma, representing a category of kidney cancer that is responsible for 5%-10% of all kidney cancer deaths each year. In order to design better therapeutic strategies for patients with papillary renal cell carcinoma, we first need to study how this form of kidney cancer develops from healthy cells of the kidney and identify ways to interfere with the growth of tumor cells. Unfortunately, the kidney cancer community does not currently benefit from sufficient models to study how papillary renal cell carcinoma develops. If we can generate models of papillary renal cell carcinoma to use in the laboratory setting, we can then test different strategies to impair tumor growth ultimately translating into better patient outcomes. Objective/Aims: The goal of this project is to develop new models of papillary renal cell carcinoma, so that we can study how tumors develop and identify therapeutic strategies in the future including therapies that boost the patient s own immune system called checkpoint inhibitors. Using a novel approach successfully employed in other cancers, we will develop preclinical models of papillary renal cell carcinoma using both mouse and human kidney cells. Tumors arising from both mouse kidney cells and human kidney cells will be grown inside of mice to mimic a living environment. Areas of Emphasis: This proposal will help us to increase understanding of the biology of kidney cancer by generating new models to study how papillary forms of kidney cancer develop from normal cells. How will this help patients? Our study will be most helpful for individuals who have a form of kidney cancer called papillary renal cell carcinoma. We anticipate that our models will significantly aid in the development and testing of therapies for papillary renal cell carcinoma, may help us understand which patients are likely to respond to which treatment options, and better understand resistance mechanisms to current forms of therapy. Timeline: The proposed research and development of models of cancer will not only serve as a resource for testing of current and future treatments, but it may also lead to identification of new targets or biomarkers to help aid patient care. The models will take at least one year to develop, followed by several years to interrogate those models and test therapeutics. The likely clinical application of this research is at least 3-4 years away. However, in the absence of these models, there is limited capacity to test therapeutics in papillary kidney cancer, highlighting the importance of this research. Contributions to kidney cancer research: We will generate new models of papillary renal cell carcinoma, which we will distribute to the research community and that can be used to understand (1) what factors contribute to the development of kidney cancer and (2) which therapeutic strategies may be useful to slow tumor growth. Relevance to Military Health: The proposed research will move us closer to testing new treatments that can help military Service Members, Veterans, and their family members suffering from papillary forms of kidney cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110848
Entities
People
- Andrew Goldstein
Organizations
- United States Army
- University of California, Los Angeles