Ephrin receptor B2 (EPHB2)-driven ST ependymoma models—also highly expressed in ST-EPN-RELA tumors—have pinpointed 5-fluorouracil treatment as a potential cytotoxic therapy with efficacy in murine models and is currently being evaluated in early phase ependymoma clinical trials [1, 16, 38]. The gene discussed is EPHB2; the disease is ependymoma.