EPN-26: ONCOLOGY DRUG SCREEN IDENTIFIES EPENDYMOMA-SELECTIVE POTENCY OF 5-FU ANALOGS AND mTOR INHIBITORS

Chemotherapy has yet to show reproducible therapeutic benefit in ependymoma, and this is partly due to a lack of models for preclinical testing. Treatment of ependymoma has therefore changed little over the last 40 years and is essentially limited to surgery and radiation. Recurrence risk is high, particularly in those ependymoma harboring chromosome 1q gain. Our group has recently succeeded in establishing 2 posterior fossa 1q+ ependymoma cell lines which provides a model for high throughput testing of therapeutic treatments. With the goal of immediate clinical translation, we screened these cell lines and for ependymoma-selective drug sensitivity across a panel of 124 FDA-approved oncology drugs. Treatment effect was measured using a tritiated-thymidine incorporation proliferation assay and ependymoma-selective sensitivity was determined by comparison to a panel of other pediatric brain tumor types (medulloblastoma, glioblastoma, DIPG and AT/RT). Using this approach we identified 8 compounds that were significantly (p < 0.05) more potent in ependymoma than controls. Of note, 3 of these target mTOR (everolimus, temsirolimus and rapamycin), a therapy that is currently in phase 2 clinical trial for recurrent ependymoma. The single most ependymoma-selective drug was 5-FU analog floxuridine, a class of drug that has previously been identified as ependymoma-selective in an ependymoma mouse model and is also being evaluated clinically. Conversely, vinca alkaloids showed lower potency in ependymoma compared to other tumor types. These findings support further clinical evaluation of 5-FU analogs and mTOR inhibitors as effective chemotherapeutics for ependymoma.