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.

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Can Zika Be Used To Fight Glioblastoma Brain Tumors?

MedicalResearch.com Interview with:

Milan G. Chheda, MD Assistant Professor  Department of Medicine  Oncology Division  Molecular Oncology  Department of Neurology Washington University School of Medicine in St. Louis

Dr. Chheda

Milan G. Chheda, MD
Assistant Professor
Department of Medicine
Oncology Division
Molecular Oncology
Department of Neurology
Washington University School of Medicine in St. Louis

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Glioblastoma is an extremely aggressive brain tumor. Most patients die in less than two years. A longstanding challenge has been killing tumor cells that are inherently resistant to our current therapies (radiation and chemotherapy). These cells, called cancer stem cells, are extremely hardy. A longstanding dream of oncologists has been to devise a way to find them and kill them. The public health epidemic in 2015 made Zhe Zhu, post-doctoral fellow in Jeremy Rich’s lab, wonder whether Zika virus could work on cancer stem cells, that share properties with stem cells in fetal brain. Zika virus doesn’t cause significant problems in adults.

We took a lesson from nature and tested Zika virus.

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Akt3 Protein Makes Brain Tumor Resistant To Treatment

MedicalResearch.com Interview with:
Kristen Turner PhD. (first author) and
Wei Zhang, Ph.D. Professor
Department of Pathology
Director, Cancer Genomics Core Lab
University of Texas MD Anderson Cancer Center
Houston, Texas 77030

Medical Research: What is the background for this study? What are the main findings?

Response: Glioblastoma (GBM) is the most commonly diagnosed type of brain tumor and is among the most aggressive and challenging cancer types to treat. The traditional approaches to combat this pervasive cancer include surgery combined with radiation and chemotherapy (temozolomide); yet, most will succumb to the disease in just over one year.

In this study, we investigated the Akt family of proteins that are known to be highly active in the majority of Glioblastoma cases. We compared each Akt family member and its ability to initiate glioma progression. We discovered that activation of the third Akt member (Akt3) led to glioma progression and very aggressive tumors. We then studied these tumors to compare their molecular attributes and found evidence of increased DNA repair. Finally, we discovered that the Akt3-induced DNA repair function led to increased survival of Glioblastoma cells after treatment with the DNA damaging agents, radiation and temozolomide. Continue reading

Recurrent Glioblastoma: Treatment with Cytomegalovirus Immunotherapy

MedicalResearch.com Interview with:
Dr Andrea Schuessler
QIMR Berghofer Medical Research Institute
Herston, Queensland 4006

MedicalResearch.com: What are the main findings of the study?

Dr . Schuessler: Recurrent glioblastoma is a very aggressive brain cancer and most patients do not survive much longer than 6 months. Our study has assessed a novel immunotherapy and treated 10 patients with late stage cancer. The treatment did not have any serious side effects and most of the patients have survived much longer than the expected 6 months. Importantly, four of the 10 patients have not shown signs of disease progression during the study period with one of them still being cancer free four years after the treatment.
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Glioblastoma: Avastin Did Not Improve Survival or Symptoms

Minesh P. Mehta, M.B., Ch.B. F.A.S.T.R.O. Professor of Radiation Oncology, University of Maryland School of Medicine Radiation oncologist, University of Maryland Marlene and Stewart Greenebaum Cancer Center, Chair, RTOG brain tumor committeeMedicalResearch.com Interview with:
Minesh P. Mehta, M.B., Ch.B. F.A.S.T.R.O.
Professor of Radiation Oncology,
University of Maryland School of Medicine
Radiation oncologist, University of Maryland Marlene and Stewart Greenebaum Cancer Center

MedicalResearch.com: What are the main findings of the study?

Dr. Mehta: RTOG 0825 was a clinical trial evaluating whether the addition of a novel drug that inhibits tumor vascular growth, bevacizumab, to the standard of care for glioblastoma, an aggressive brain tumor, would prolong survival. Patients were allocated randomly to one of two different treatment regimens – the standard of care, which includes radiotherapy and a drug known as temozolomide, or another regimen of radiation, temozolomide and bevacizumab. The trial design was double-blinded, and therefore, on one arm patients received the bevacizumab, whereas on the other arm they received a placebo. The survival on both arms was equivalent, and therefore it was fairly concluded that bevacizumab failed to prolong survival when given initially as part of treatment for glioblastoma.

Freedom from progression, referred to as progression-free survival was also measured on this trial, and although bevacizumab appeared to lengthen progression-free survival, this level of benefit did not meet the pre-defined goals, and is therefore regarded as statistically not demonstrating an improvement.

Additional endpoints included outcomes reported by the patient, including the burden of symptoms, and the impact of these on the quality of life, as well as effects on the brain, known as neurocognitive changes. Bevacizumab did not improve these endpoints either.

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