Developing Clinically Relevant Genetic Mouse Models for Upper Track Urothelial Cancer
Abstract
Background and scientific objective: Upper tract urothelial carcinoma (UTUC), a rare cancer type that occurs in the urinary system, including kidney, accounts for approximately 10% of renal tumors and 5% of all urothelial carcinomas. The treatment options for UTUC are still limited to chemotherapy and surgery and patients with advanced UTUC remain incurable. There is an urgent need to develop better therapeutic strategies. However, our understanding of UTUC development and progression remains limited. Recent studies of human UTUC have led to the identification of changes in patients genomic DNA sequences. Although patient-derived xenografts (PDXs) and cell lines generated from human UTUCs serve as valuable research tools, they cannot be easily used to study the impact of the immune system on UTUC progression and on the responses of UTUC to various cancer therapies, including immunotherapy. Currently, there are no genetic mouse models for UTUC, which hampers our efforts to fully harness the power of immunotherapy to achieve durable control or cure of UTUC. Thus, there is an unmet need to develop UTUC genetically engineered mouse models. The objective of this study is to develop clinically relevant UTUC GEMMs, which will facilitate basic and translational research. Innovation: Our proposed study will lead to the development of a novel UTUC genetic mouse model and cell lines harboring clinically relevant genetic aberrations. Also, our study will provide novel insights into the molecular and cellular process driving UTUC progression. Impact: In the short term, our proposed research will lead to a better understanding of how UTUC develops and progress to advanced stages. Also, our study will lead to the generation of new research tools for preclinical research, which will allow researchers to study the functions of UTUC-related genes and test novel therapeutics. Ultimately, our study will improve the clinical outcome of UTUC in the long term.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310305
Entities
People
- Guocan Wang
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army