The Mechanistic Underpinnings of Pancreatic Neuroendocrine Tumors
Researcher: Guillermina Lozano, PhD Location: MD Anderson Cancer Center State: Texas Year: 2016 Status: Active
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The objective of this project is to generate and characterize mouse models to better understand pancreatic neuroendocrine tumors and the cooperating events that contribute to tumor development. A faithful animal model will be invaluable for identifying novel vulnerabilities and therapeutic targets for pancreatic neuroendocrine tumors.
Dr. Lozano’s laboratory has extensive experience in generating mouse models to study the effects of specific mutations on tumor development. Previous NETRF-funded researchers discovered mutations in the DAXX and ATRX genes in tumors from patients with non-functioning pancreatic neuroendocrine tumors. Despite these 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 other epigenetic regulators to determine the impact of these mutations on tumor growth.
NETRF is pleased to recognize Dr. Lozano as a Petersen Investigator, with generous support for this grant provided by the Margie and Robert E. Petersen Foundation.
Define the role of DAXX as an epigenetic regulator in the endocrine and exocrine pancreas.
Evaluate the pathological consequences and potential for tumorigenesis downstream of DAXX loss.
Because of their rarity, pancreatic neuroendocrine tumors are not well studied and treatment options are limited. Recently, the sequencing of the DNA from these cancers has revealed recurring mutations in six specific genes, three of which encode proteins that may have global effects on gene expression. This proposal aims to generate and characterize mouse models to better understand the etiology of the disease and the cooperating events that contribute to tumor development.
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