Non-Mammalian Animal Models with Glioma for Cancer Discovery

Inventors: Renee D. Read and John B. Thomas
Potential Uses: Drug Discovery and Development, Oncology

EGFR;PI3K induces glial neoplasia demonstrated with Pnt and Stg expression. Optical projections of whole brain-ventral nerve cord complexes from late 3rd instar larvae of the indicated genotype, approximately 130 hr AED, all matched in scale. CD8GFP (green) expression in all repo-Gal4-expressing glia reveals structure of the entire CNS. 200 mm scale bar

Gliomas, neoplasms of glial cells and their precursors, are the most common malignant tumors of the central nervous system (CNS). These tumors typically proliferate rapidly, diffusely infiltrate the brain, and resist standard therapies, properties that render them largely incurable. One key to developing more effective therapies against these tumors is to understand the genetic and molecular logic underlying gliomagenesis. Gliomas frequently harbor mutations that activate the epidermal growth factor receptor (EGFR) and phosphatidylinositol-3 kinase (PI3K) signaling pathways. To investigate the genetic basis of this disease, we developed a glioma model in Drosophila. We found that constitutive coactivation of EGFRR and PI3K pathways in Drosophila glia and glial precursors gives rise to neoplastic, invasive glial cells that create transplantable tumor-like growths, mimicking human glioma. Our model represents a robust organotypic and cell-type specific Drosophila cancer model in which malignant cells are created by mutations in signature genes and pathways thought to be driving forces in a homologous human cancer. These models prove useful for both discovering new oncology treatments and new genes associated with this disease.