MedicalResearch.com Interview with:
Bakhos Tannous, PhD
Department of Neurology
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Glioblastoma (GBM) is the most common and most aggressive type of brain tumors in adults. Over the last two decades, the major improvement in the treatment for GBM has been the addition of the chemotherapeutic temozolomide (TMZ) to the standard of care (surgery and radiation), however, despite this aggressive therapy, over 90% of patients die within five years after diagnosis. Further, only about half of GBM patients really benefit from TMZ treatment, while the other half are somewhat resistant to TMZ since their tumor endogenously carry a DNA repair mechanism that removes DNA adducts caused by TMZ.
We therefore wanted to find a combination therapy that overcomes TMZ resistance and works in all GBM patient populations, with a fast transition to the clinic. Through a repurposing drug screening aiming at recycling of old known drugs for new therapies, we found that the FDA-approved drug hydroxyurea to synergizes with temozolomide in patient-derived GBM cells from newly diagnosed and recurrent tumors, irrespective of their DNA repair mechanism. The combination of hydroxyurea and TMZ worked very well in all different patient cell population tested, and was not specific to one subtype, and lead to a significant increase in survival rate in different mouse models.