Intratumoral Activity Of Onc201 In Adult Recurrent Glioblastoma Patients
JOURNAL OF CLINICAL ONCOLOGY(2018)
Abstract
e14034Background: ONC201 is an antagonist of the G protein-coupled receptor DRD2 that crosses the blood-brain barrier and induces tumor cell apoptosis in preclinical models. The anti-tumor activity of ONC201 is pronounced in cells with low DRD5 expression and is associated with induction of the ATF4/CHOP/DR5-mediated integrated stress response pathway to trigger apoptosis. We previously reported the single agent activity of ONC201 in 17 adult patients with recurrent glioblastoma that demonstrated the safety, systemic pharmacodynamics, and a durable objective response when administered orally once every 3 weeks. Here, we evaluated the intratumoral drug concentrations and pharmacodynamic activity of ONC201 in adult recurrent glioblastoma patients who were treated on a weekly schedule. Methods: Six patients ≥18 years old with first recurrence of glioblastoma who were eligible for salvage surgical resection were enrolled. ONC201 was administered orally as 625 mg once a week. Salvage surgery was performed appr...
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Cancer Cell Metabolism
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