Preclinical precision targeting of major driver mutations in childhood Diffuse Intrinsic Pontine Giloma
Abstract
My career goal in cancer research is to contribute towards finding a cure for diffuse intrinsic pontine gliomas (DIPGs) by effectively conducting research studies using cells and mice in order to develop promising clinical trials. The Peer Reviewed Cancer Research Program Horizon Award will provide an avenue for outstanding training to conduct focused research to discover an effective therapy for children affected by DIPGs. This award will help immensely towards my development as a cancer researcher by formulating research questions, designing experiments, analyzing data, and applying findings to establish a clinically relevant treatment option for DIPG patients. I am currently conducting my research in Dr. Nazarian’s laboratory, where I will learn more molecular biology techniques to execute my research design. Dr. Nazarian works closely with clinicians and physician-scientists at Children s National Health System, as well as collaborators around the world who have expertise in neurosurgery, neuropathology, and clinical trials in neuro-oncology. Therefore, I have the opportunity to interact with experts in the field to learn how to apply my research to a clinical setting. DIPG is a deadly brain tumor that affects about 200-300 children every year in the United States. Sadly, most of these patients do not survive for more than about 1 year after being diagnosed. Current therapy for DIPGs is ineffective because of the poor understanding of the biology of this particular type of cancer. Our group recently published a study showing that DIPGs have unique mutations in their genes. The proposed research project focuses on using laboratory models of DIPG to test drugs for targeting genomic mutations that seem to cause the disease. Specifically, we will target mutations that affect two genes known as H3F3A and TP53. These two genes are mutated in over 50% of patients with DIPG. Our plan is to use drugs to target these two genes, first using tumor cells growing in petri dish, and then in mouse models of DIPG. The uniqueness of our proposal is the use of combinations of multiple drugs as a treatment regime. The strength of our study is that we can test a large number of drug combinations in petri dishes that would be almost impossible in humans. These data will be tested further in mouse models where tumor growth will be monitored as a response to treatment. Among the five drugs that are being tested in this study, four of these have already been approved by the Food and Drug Administration (FDA). Therefore, there is potential for these research findings to be rapidly applied to the clinic, within the next 5 years. This study will help clinicians to provide DIPG patients with drug treatments that are more promising than what is currently available to them. The 200-300 cases of DIPG patients diagnosed every year includes children in military families who have suffered from this disease. The dismal prognosis of DIPG is a burden on military families, and there is a great need for new and effective therapy. Therefore, the findings of this research study will directly benefit active duty Service members and their families.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710499
Entities
People
- Eshini Panditharatna
Organizations
- United States Army