Repurposed Drug Hydroxyurea May Improve Glioblastoma’s Response to Chemotherapy

MedicalResearch.com Interview with:

Bakhos Tannous

Dr. Tannous

Bakhos Tannous, PhD
Neuro-Oncology Division
Department of Neurology
MGH

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.

 

MedicalResearch.com: What should readers take away from your report?

Response: Combining hydroxyurea with TMZ for the treatment of GBM could be highly beneficial for these patients, which could lead to an increase in their survival rate. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

 Response: Since the combination of hydroxyurea and TMZ showed to be very efficient in all pre-clinical models tested, it should now be tested in humans. As a matter of fact, we are preparing to evaluate this combination therapy in a phase I clinical trial.

Citations:

Recycling drug screen repurposes hydroxyurea as a sensitizer of glioblastomas to temozolomide targeting de novo DNA synthesis, irrespective of molecular subtype.

Teng J, Hejazi S, Hiddingh L, Carvalho L, de Gooijer M, Wakimoto H, Barazas M, Tannous M, Chi AS, Noske DP, Wesseling P, Wurdinger T, Batchelor TT, Tannous BA. Recycling drug screen repurposes hydroxyurea as a sensitizer of glioblastomas to temozolomide targeting de novo DNA synthesis, irrespective of molecular subtype. Neuro Oncol. 2017 Nov 01.

 

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One thought on “Repurposed Drug Hydroxyurea May Improve Glioblastoma’s Response to Chemotherapy

  1. Congratulations on successfully pursuing this principle, presumably building on studies from around 2005. Some cells are also killed in S-phase by hydroxyurea — did this happen in any of the lines you tested? If so, hydroxyurea should also be given during radiation treatment for reducing the most resistant (S-phase) cell population. Might it be interfering with scavenger pathways used by surviving GBM cells following autophagy as well? Would it be useful to add chloroquine to the mix in one arm of a clinical study to explore the impact of inhibiting autophagy? Glioblastoma is terrible; everything within reason needs to be tried.
    It would be a privilege to receive a reply from you.
    Keep up the good work
    Paul Todd

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