Glioblastoma is an aggressive
central nervous system tumor with a 5-year-survival rate of less than 10%. Patients diagnosed with the disease are treated with surgery, radiation and
temozolomide chemotherapy. Despite survival benefits, patients eventually relapse. There is a need for new treatments with improved efficacy. Imipridone
ONC201 is a small molecule originally identified as a
TNF-related apoptosis inducing ligand (TRAIL)-inducing compound.
ONC201 has the unique ability to induce expression of both pro-death
ligand TRAIL and its
receptor DR5 through engagement of the cellular integrated stress response (ISR) pathway. Arrillaga-Romany et al. report early results from futility analysis of a phase II clinical trial of
ONC201 in 17 patients with recurrent or refractory
glioblastoma conducted at the Massachusetts General Hospital
Cancer Center. The results are promising, as
ONC201 shows preliminary signs of efficacy. Further testing of
ONC201 in an expansion cohort of patients with
glioblastoma is ongoing.