LW-10 PRECLINICAL THERAPEUTIC TESTING FOR BRAIN TUMOR USING PATIENT-DERIVED XENOGRAFT (PDX) MODEL

Abstract

Abstract I have been working on the brain tumor research about 20 years in the United State. My primary research interests in understanding of the mechanisms of genetic and epigenetic regulation that promote tumor development and progression, and identify novel therapeutic targets for the treatment of human brain cancer. For these purposes, I have developed many unique patient-derived xenograft (PDX) models for human brain tumors in the brains of immunocompromised mice. This animal model system has been shown to better preserve tumor characteristics, as manifested in patients, than tumor cell propagation in cell culture. In association with the development of these models, my laboratory utilizes numerous techniques to investigate brain tumor growth and response to novel agents that are administered singularly or in combinations, including with radiation. My laboratory employs the latest genomic/epigenomic technologies to identify novel genetic and epigenetics alteration that would reveal rational therapeutic targets, and test the anti-tumor activity of the therapeutics using PDX mouse model including diffuse intrinsic pontine glioma (DIPG) harboring histone H3 gene mutation (H3K27M). We have investigated the role of H3K27M mutations and histone modifications, and preclinical therapeutic testing in DIPG PDX models. In addition to the molecular targeted therapy, we recently implement AI machine learning approach and emerging patient genomic data to discover more effective and less toxic candidates from billions of compounds for brain tumor therapy. Moreover, we investigate new drug delivery systems to bypass the blood-brain barrier using convection-enhanced delivery and intranasal delivery. My long-term goal of my work further tests the efficacy of my approach preclinically and, if validated, move this therapeutic approach to clinical trial. In the meeting, I will present current advances in experimental therapeutics in my laboratory.