Interrogation of the KDM1A-IL18 Axis in Pediatric High-Grade Glioma
Abstract
Diffuse Intrinsic Pontine Glioma (DIPG) is a type of high-grade glioma that remains uniformly fatal in 2022, represents the leading cause of death for pediatric brain tumor patients, and for which the standard of care has not improved in over 50 years. In addition, despite at least 100 clinical trials, there is not a single drug that has been shown to significantly prolong the survival of children with DIPG beyond radiation alone.The objective of our study is to unravel the role of LSD1 or KDM1A in DIPG pathogenesis focusing on its effect on immune related genes. We hypothesize that LSD1 promotes gliomagenesis in part by repressing immune-related genes such as IL18, and that inhibition of KDM1A will be efficacious in prolonging the survival of DIPG-bearing mice, in part through upregulation ofIL18, thereby altering the tumor microenvironment. At the end of year 1, we have made progress toward accomplishing the Statement of Work and our data suggests that LSD1 is a bone-fide therapeutic target in DIPG. In the upcoming two years we will clarify the mechanism and prioritize a drug and potentially a combination for clinical translation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1226278
Entities
People
- Oren Becher
Organizations
- Icahn School of Medicine at Mount Sinai