Previous NETRF-funded researchers discovered mutations in the genes DAXX and ATRX among tumors from patients with non-functioning pancreatic neuroendocrine tumors. Despite these exciting and promising findings, the precise role of ATRX and DAXX in neuroendocrine tumor development is yet to be understood and treatments exploiting these findings have yet to be developed. Furthermore, researchers do not have the research tools they need to develop potential new therapies for patients exploiting these mutations. In this project, Dr. Lozano will create the mouse models necessary to identify the cellular changes that occur with loss of DAXX and ATRX to determine the impact of DAXX and ATRX mutations on tumor growth. The mouse models that the team creates will both define the importance of the p53 pathway in the maintenance of pancreatic neuroendocrine tumors and be useful to test potential new therapies.
Wasylishen AR, Estrella JS, Pant V, Chau GP, Lozano G. Daxx Functions Are p53-Independent In Vivo. Mol Cancer Res. 2018 Oct;16(10):1523-1529. doi: 10.1158/1541-7786.MCR-18-0281. Epub 2018 Jun 14.