Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial.

ABSTRACT:

Purpose

High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role.

Experimental design

In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood-brain barrier di

SUBMITTER: Xu R 

PROVIDER: S-EPMC5050072 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature