Targeting Neuroendocrine (Androgen and Aromatase) Pathways for the Treatment of Pediatric Pontine Gliomas

Background

Approximately 300 children in the U.S are diagnosed with Diffuse intrinsic pontine glioma (DIPG), which is a universally fatal brain cancer affecting children between the ages 5 and 9. There are minimal treatments for this, as surgery is not an option, the effects of radiation therapy of temporary, and no chemotherapeutic agent has demonstrated significant efficacy. In a recent preliminary drug screen of 114 FDA-approved cancer drugs against DIPG cells, a group of compounds commonly used in treatment of androgen-receptor (AR) and aromatase(CYP19A1) driven prostate and breast cancers were identified, and they show significant growth inhibition of DIPG.

Project Goal

Dennis will be working to test the hypothesis that AT and CYP19A1 have a role in DIPG tumorigenesis and progression, similar to other malignancies. The research plan will aim to target these receptors for DIPG growth and progression in cancer cells and in mice models. Also, they will perform the FDA-approved drug screen on a panel of at least 10 patient-derived DIPG cell lines established in our laboratory, as well as obtained from our collaborators nationwide. This work will help them in further delineation possible potential effective therapeutic molecules for DIPG, and help them understand the biological and clinical significance of Ar and CYP19A1 and validate them as potential targets for DIPG therapy. If this project is successful, it will help rapidly repurpose already FDA-approved drugs to be applied to children with DIPG in clinic.