Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of
brain cancer. Despite progress in development of novel
therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that
oleandrin, a unique
cardiac glycoside from Nerium oleander, as well as a defined extract (PBI-05204) that contains this molecule, inhibit growth of human
glioblastoma, and modulate
glioblastoma patient-derived stem cell-renewal properties. Here we demonstrate that
PBI-05204 treatment leads to an increase in vitro in the sensitivity of GBM cells to radiation in which the main mechanisms are the transition from autophagy to apoptosis, enhanced DNA damage and reduced DNA repair after
radiotherapy (RT) administration. The combination of
PBI-05204 with RT was associated with reduced
tumor progression evidenced by both subcutaneous as well as orthotopic implanted GBM
tumors. Collectively, these results reveal that
PBI-05204 enhances antitumor activity of RT in preclinical/murine models of human GBM. Given the fact that
PBI-05204 has already been examined in Phase I and II clinical trials for
cancer patients, its efficacy when combined with standard-of-care
radiotherapy regimens in GBM should be explored.