Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Immunotherapy, Pharmaceutical Companies / 22.02.2021 Interview with: Skolnik, MD Senior Vice President, Clinical Development INOVIO What is the background for this technology? Would you tell us a little about the brain tumor, Glioblastoma Multiforme? How common is it, whom does it primarily affect?  Response: Glioblastoma (GBM) is the most common malignant brain tumor, affecting more than 10 thousand people each year in the United States. Most people diagnosed with GBM are above the age of 60 years, although GBM can be diagnosed at any age, including in children and young adults. Despite decades of research, GBM remains almost universally fatal. GBM is a tumor of the glial cells of the brain, and current therapies are directed at removing tumor with surgery and killing residual tumor cells with radiation and chemotherapy. More recently, with the introduction of immunotherapies such as immune checkpoint inhibitors (ICI) for the treatment of cancer, clinical studies have tried to add this promising technology to the treatment of GBM. Unfortunately, despite success in other types of cancer, ICIs have not demonstrated any clinical benefit in treating GBM. Newer clinical studies aim at introducing a combination of newer therapies together to try to tackle this terrible disease, and INOVIO’s GBM-001 study is one such example of an innovative approach to treating GBM.    (more…)
Author Interviews, Brain Cancer - Brain Tumors, Imperial College / 20.08.2019 Interview with: Georgios Giamas, (Dr. Biol. Hum.) Professor of Cancer Cell Signalling Director of Research and Knowledge Exchange University of Sussex -School of Life Sciences Visiting Professor, Imperial College, London What is the background for this study? Response: This study focuses on Glioblastoma (GBM), which is one of the most aggressive solid tumours for which treatment options and biomarkers are limited. What are the main findings? - Glioblastoma cells produce nanosized vesicles (aka: extracellular vesicles) that contain specific protein signatures, which can indicate the behaviour and phenotype of the respective cells of origin. -We have identified and described certain vesicle-associated biomarkers that correspond to the most aggressive brain cancers. -Our results can provide insights for the development of new diagnostic and therapeutic methods as well as personalized treatment strategies (more…)
Author Interviews, Cancer Research, Genetic Research / 08.04.2019 Interview with: Eunhee Yi, Ph.D. Postdoctoral Associate The Jackson Laboratory What is the background for this study? What are the main findings?  Response: Recurrence after therapy for glioblastoma (GBM) is unavoidable. There are substantial differences among the cells of GBM tumors in the abundance and types of genetic materials. This heterogeneity is a major driver of therapy failure and disease progression. We previously reported that extrachromosomal DNA (ecDNA) elements, which reside outside the linear genome and represent a mechanism to amplify and activate oncogenes, is a potential cause of the increasing genetic diversity in GBM. Our current study is focused on the development of a novel cytogenetic tool to visualize ecDNA to visualize the behavior of these elements in live cells. We have leveraged the unique properties of ecDNA to develop a CRISPR-based “ecDNA tracing toolbox (EDTB)”.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 22.01.2018 Interview with: Bakhos Tannous, PhD Neuro-Oncology Division Department of Neurology MGH 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. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Zika / 07.09.2017 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 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. (more…)
Author Interviews, Cancer Research, MD Anderson, PNAS / 04.03.2015 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. (more…)
Author Interviews, Brain Cancer - Brain Tumors / 05.05.2014 Interview with: Dr Andrea Schuessler QIMR Berghofer Medical Research Institute Herston, Queensland 4006 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. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, NEJM / 22.02.2014

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 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 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. (more…)