Targeting the Polycomb Pathway for Testicular Cancer Therapy in Adolescents and Young Adults
Abstract
We are encouraged by our generated data thus far that our hypothesis that the polycomb pathway plays a major role in cisplatin sensitivity and resistance in testicular germ cell tumors (TGCTs) is correct. The purpose of this project is to validate this concept and to provide data on mechanism and to uncover biomarkers of response to support future clinical trials targeting the polycomb pathway in TGCT patients. The major findings in this first funding period have shown that targeting the polycomb pathway both pharmacologically and genetically alters cisplatin sensitivity of TGCT in vitro and targeting the polycomb pathway pharmacologically alters cisplatin sensitivity in vivo in mice. We have also obtained and have begun to establish the genetically engineered mouse model in the lab, which will help to further validate the biological significance of polycomb as a therapeutic target in TGCTs. In terms of mechanism and biomarker identification we have performed a number of unbiased genome-wide studies including RNA-seq,H3K27me3 ChIP-seq and p53 ChIP-seq. We are still analyzing and integrating this data and have more genome-wide studies to perform to get a more complete picture of how polycomb is mediating cisplatin sensitivity in TGCTs. We have also collected the TGCT patient samples for this study and have made good progress in assessing the most direct biomarker, H3K27me3, in this cohort. We have not encountered any insurmountable issues in any of the original goals of the project and are on track to complete all the tasks as outlined in the original proposal and the SOW. Our results to date strongly support that polycomb may be a valuable and useful therapeutic target to treat cisplatin refractory TGCTs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1190496
Entities
People
- Michael Spinella
Organizations
- University of Illinois Urbana–Champaign