Dissecting the Role of FOXR2 in the Oncogenesis of Diffuse Intrinsic Pontine Glioma
Diffuse intrinsic pontine glioma (DIPG) is a deadly pediatric brain cancer. Despite radiation treatment, the current standard of care, almost all children diagnosed with the disease succumb to it with a median survival of 12 months. There have been few advancements in treatment, and current treatment has no curative intent. Therefore, there is a significant need to develop new therapeutic strategies to improve the terrible outcomes for these children and improve quality of life for patients and their families. Looking at genes that are turned on or off in a particular type of cancer can be helpful to figure out what is causing the cancer to grow. One such gene which we found to be turned on in DIPGs is FOXR2, which has also been described to help other cancers grow. In this project, I will study how this gene FOXR2 contributes to growth of DIPG cells in order to help us understand how we can therapeutically target it.
Project Goal:
This goal of this project is to figure out exactly how the gene FOXR2 makes DIPGs grow. We have used a new mouse tumor model system, and we know that FOXR2 makes gliomas grow extremely quickly and the mice develop symptoms of DIPG. We will figure out first if FOXR2 is able to cause increased cell growth and tumor formation using both mouse models and cell culture models of DIPG. We will then determine what other pathways FOXR2 turns on or off to promote growth. Understanding how FOXR2 activates different pathways will be important to find new treatments. Ultimately, we have found a new genetic alteration called FOXR2 that is present in a subset of DIPGs. The goal of this work is to understand how this gene increases tumor growth and aggressiveness with the goal of identifying new therapeutic targets and treatments for this devastating disease.
Project Update 2024:
Diffuse intrinsic pontine glioma (DIPG) is a deadly pediatric brain cancer. Despite radiation treatment, the current standard of care, almost all children diagnosed with the disease succumb to it with a median survival of 12 months. There have been no advancements in treatment, and current treatment has no curative intent. Therefore, there is a significant need to develop new therapeutic strategies to improve the terrible outcomes for these children and improve quality of life for patients and their families. Looking at genes that are turned on or off in a particular type of cancer can be helpful to figure out what is causing the cancer to grow. One such gene which we found to be turned on in DIPGs is FOXR2, which is thought help a number of cancers grow. In this project, we studied how the gene FOXR2 contributes to the growth of DIPG cells in order to help us understand how we can therapeutically target it. We confirmed that FOXR2 is able to cause increased cell growth and tumor formation using both mouse models and cell culture models of DIPG. We then sought to determine what other pathways FOXR2 turns on or off to promote growth. Understanding how FOXR2 activates different pathways is necessary in order to find new therapies to help treat this terrible disease.
