Author Interviews, Brain Cancer - Brain Tumors, Cancer Research / 09.08.2023

MedicalResearch.com Interview with: Sibaji Sarkar, Ph.D. Division of Biotech, Quincy College Quincy MA. Biology/STEM MBC College, Wellesley MA, Boston MA. MedicalResearch.com: What is the background for this study? What are the main developmental differences between adult and pediatric tumors? Response: The treatment of both pediatric and adult types of brain tumors is complex.  The treatment and prognosis depend on their origin, development, progression and location. It is extremely important that the origin, which involves formation of cancer stem/progenitor cells, is investigated to understand growth, drug resistance and relapse of the brain tumors. Pediatric brain tumors often are less metastatic and treatable but chemo leaves adverse effects for longer times. Adult metastatic brain tumors usually have worse prognosis. To understand and develop better treatments we need to understand the differences in the origin and progression of these different types of brain tumor [1]. One of the important aspects is epigenetic alterations. Epigenetic alterations are reversible and different from mutations in genes, which are usually permanent. In epigenetic alterations, modifications occur on DNA or the protein histones around which the DNA is folded and they regulate whether a gene will express or not (will make a protein or not), that determines a special function. (more…)
AACR, Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Pediatrics / 10.04.2021

MedicalResearch.com Interview with: Gregory K. Friedman, MD Associate Professor Director, Developmental Therapeutics Associate Scientist, O'Neal Comprehensive Cancer Center at UAB Neuro-Oncology Program Division of Pediatric Hematology-Oncology University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? Response: This was a first-in-children trial to test the safety of an immunotherapy using an altered cold-sore virus (herpes virus or HSV-1), G207, infused directly via catheters into progressive or recurrent malignant brain tumors. Due to modifications in G207, the virus does not harm normal cells but can infect and directly kill tumor cells while also stimulating the patient’s own immune system to attack the tumor. We tested G207 at two dose levels alone and when combined with a single low dose of radiation, which was used to increase virus replication and spread throughout the tumor. The research is important because outcomes are very poor for children with progressive malignant brain tumors, and the toxicities caused by current standard therapies are unacceptably high. Therefore, we greatly need effective and less-toxic targeted therapies for children. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Immunotherapy, Pharmaceutical Companies / 22.02.2021

MedicalResearch.com Interview with: https://www.inovio.com/Jeffrey Skolnik, MD Senior Vice President, Clinical Development INOVIO MedicalResearch.com: 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

MedicalResearch.com 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 MedicalResearch.com: 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. MedicalResearch.com: 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, Brain Cancer - Brain Tumors, Radiation Therapy, Surgical Research / 12.11.2018

MedicalResearch.com Interview with: Dr. Stephanie E. Weiss MD FASTRO Chief, Division of Neurologic Oncology Associate Professor, Department of Radiation Oncology Director, Radiation Oncology Residency and Fellowship Training Program Fox Chase Cancer Center Philadelphia, Pennsylvania MedicalResearch.com: What is the background for this study? Response: Brain metastasis are the most common form of brain tumor. Historically all patients received whole brain radiation as the primary therapy. Patients required neurosurgery to remove lesions if there was a question of diagnosis, what the diagnosis is and if there was a mass effect not relieved with steroids. Surgery was also indicated for patients with a single brain lesion because this offers a survival benefit over just receiving whole brain radiotherapy. In 2003 a randomized trial proved that radiosurgery offers a similar benefit. So the question taxing patients and doctors at tumor boards since has been: which is better? If neurosurgery is superior, we are under-treating a lot of patients with radiosurgery. If radiosurgery is superior, we are subjecting a lot of patients to unnecessary brain surgery. Attempts to study this in a head-to-head randomized trial have failed. Patient and physician preference for one treatment or the other has proven to be a barrier to randomization and accrual. The EORTC 22952-2600 trial was originally designed to compare outcomes with and without whole brain radiation for patients receiving surgery or radiosurgery for brain metastasis. We used this as the highest-quality source data available to compare local control of brain metastasis after surgery or radiosurgery, adjusted for by receipt or not of whole brain radiation.   (more…)
Author Interviews, Biomarkers, Brain Cancer - Brain Tumors, Cancer Research, Genetic Research / 21.07.2018

MedicalResearch.com Interview with: Arnab Chakravarti MD Professor and Chair of Radiation Oncology Arthur G. James Cancer Hospital and Richard J. Solove Research Institute The Ohio State University Comprehensive Cancer Center MedicalResearch.com: What is the background for this study?   Response: Historically, the treatment for grade two gliomas has been a black box without really a standard-of-care therapy. In the past, it was really dealer’s choice, where it was based upon physician and patient preference. Either radiation alone, radiation plus chemotherapy, or chemotherapy alone, there wasn't really any data to guide therapeutic decision-making. Then about three years ago the landmark study RTOG 9802 was published, which demonstrated a survival benefit with the addition of chemotherapy to radiation versus radiation alone. That became the standard of care for the treatment of grade two gliomas. One of the tricky issues with regards to these tumors is that there's a wide range of outcomes. There are patients that succumb to disease within months, others that live decades. It's very important to personalize care for the individual patient and that's why biomarkers, prognostic and predictive biomarkers are so important. The 9802 study showed us for the general population of patients that the addition of chemotherapy to radiation improved outcomes versus radiation alone. The patient population that was selected for our study were the high-risk low-grade glioma patients. Patients who are generally over the age of 40, tumor sizes that exceeded 6 cm in terms of maximum dimension, tumors that invaded the corpus callosum, astrocytic histology of patients with neurological symptoms. These are typically the patients that were included in the study. Really the main objective of this study was to determine the efficacy of treatment compared to historical controls. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Duke, Immunotherapy, NEJM, Vaccine Studies / 26.06.2018

MedicalResearch.com Interview with: Annick Desjardins, M.D., F.R.C.P.C. Associate Professor of Neurology Associate Professor of Neurosurgery Director of Clinical Research The Preston Robert Tisch Brain Tumor Center at Duke Duke University School of Medicine Durham, NC 27710 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The poliovirus receptor (CD155) is an onco-fetal cell adhesion molecule with widespread expression in all solid tumors and particularly in primary CNS tumors (adult and pediatric). Recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO) was generated by replacing a critical piece of the genetic information from the Sabin type 1 polio vaccine, making PVSRIPO incapable of harming or killing normal brain cells, but toxic/lethal in cancer cells. In preclinical models, it has been demonstrated that the infection of tumor cells, leads to the release of danger signals, which triggers a recruitment of dendritic/CD4/CD8 T cells and a destruction of tumor cells by anti-tumor T cells. The manuscript reports the results of the phase 1 trial of PVSRSIPO in recurrent WHO grade IV malignant glioma patients. Adult patients with recurrence of a single glioblastoma lesion, 1-5.5cm in dimension, in a non-eloquent area of the brain, were enrolled on study. PVSRIPO is injected slowly over 6.5 hours directly into the tumor via a small catheter inserted via a small bur hole. Once intratumoral injection is completed, the catheter is removed and patients are observed for localized tumor inflammation, followed by tumor contraction. A total of 61 patients were treated on study, 9 patients in a dose escalation phase and 52 in a dose expansion phase. Side effects observed were in relation to the localized inflammation of the tumor and depending on the cerebral functions in close proximity to the tumor: headaches, visual field changes, hemiparesis, etc. One patient experienced a brain hemorrhage at the time of catheter removal, which triggered right sided weakness and aphasia. The patient remained alive 57.5 months after PVSRIPO infusion at data cutoff of March 20th, 2018. Two on-study death were observed, a patient died from cerebral edema and seizures, which was later found to be due to tumor progression, and one patient died from the complications of an intracranial hemorrhage while receiving anticoagulation and bevacizumab. The median overall survival among all 61 patients who received PVSRIPO was 12.5 months (95% CI, 9.9 to 15.2), comparatively to 11.3 months (95% CI, 9.8 to 12.5) in a historical control group of patients treated at Duke and who would have met eligibility on trial, would have the trial been available to them. At 24 months, the survival plateaued in patients treated with PVSRIPO with an overall survival rate of 21% (95% CI, 11 to 33) at 24 months and 36 months in PVSRIPO treated patients, while overall survival in the historical control group continued to decline, with an overall survival rates of 14% (95% CI, 8 to 21) at 24 months and 4% (95% CI, 1 to 9) at 36 months in the historical control group.  (more…)
Author Interviews, Brain Cancer - Brain Tumors, Emory, PNAS, Technology / 16.03.2018

MedicalResearch.com Interview with: Lee Cooper, Ph.D. Assistant Professor of Biomedical Informatics Assistant Professor of Biomedical Engineering Emory University School of Medicine - Georgia Institute of Technology MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Gliomas are a form of brain tumor that are often ultimately fatal, but patients diagnosed with glioma may survive as few as 6 months to 10 or more years. Prognosis is an important determinant in selecting treatment, that can range from simply monitoring the disease to surgical removal followed by radiation treatment and chemotherapy. Recent genomic studies have significantly improved our ability to predict how rapidly a patient's disease will progress, however a significant part of this determination still relies on the visual microscopic evaluation of the tissues by a neuropathologist. The neuropathologist assigns a grade that is used to further refine the prognosis determined by genomic testing. We developed a predictive algorithm to perform accurate and repeatable microscopic evaluation of glioma brain tumors. This algorithm learns the relationships between visual patterns presented in the brain tumor tissue removed from a patient brain and the duration of that patient's survival beyond diagnosis. The algorithm was demonstrated to accurately predict survival, and when combining images of histology with genomics into a single predictive framework, the algorithm was slightly more accurate than models based on the predictions of human pathologists. We were also able to identify that the algorithm learns to recognize some of the same tissue features used by pathologists in evaluating brain tumors, and to appreciate their prognostic relevance. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Zika / 07.09.2017

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 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. (more…)
Author Interviews, Baylor College of Medicine Houston, Biomarkers, Brain Cancer - Brain Tumors, Cancer Research, PNAS / 19.07.2017

MedicalResearch.com Interview with: Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, abnormal EGFR signaling is frequently observed. Treatment with the EGFR inhibitor erlotinib attempts to kill cancer cells. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance. Scientists at Baylor College of Medicine discovered that the molecule CD44s seems to give cancer cells a survival advantage. Eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib. (more…)
Author Interviews, Brain Cancer - Brain Tumors, JAMA, Radiation Therapy / 01.06.2017

MedicalResearch.com Interview with: Professor Rakesh Jalali, MD Professor of Radiation Oncology President, Indian Society of Neuro-Oncology Tata Memorial Parel, Mumbai India  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Randomized controlled trials to test the efficacy of radiotherapy techniques are challenging to perform. High-precision conformal techniques such as stereotactic radiosurgery/radiotherapy, intensity modulated radiotherapy (IMRT) and particle therapy, etc have been incorporated into routine clinical practice including for brain tumors without always being supported by level-1 evidence. We therefore conducted a prospective, randomized, controlled trial of stereotactic conformal radiotherapy compared to conventional radiotherapy in young patients with residual/progressive bening and low grade brain tumors requiring radiotherapy for optimal disease control. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Radiation Therapy / 20.02.2017

MedicalResearch.com Interview with: N. Scott Litofsky, M.D. Chief of the Division of Neurological Surgery University of Missouri School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Radiosurgery is being used more often for treatment of brain metastases to avoid potential side effects of whole-brain radiation, such as cognition and mobility impairment. After surgical resection of a brain metastases, some radiation treatment is generally needed to control brain disease. Few studies have directly compared efficacy of tumor control between surgery followed by whole-brain radiation and surgery followed by radiosurgery. Our objective was to compare outcomes in two groups of patients – one whose brain metastasis was treated with surgery followed by whole-brain radiation and one whose surgery was followed by radiosurgery to the post-operative tumor bed. We found that tumor control was similar for both groups, with survival actually better in the radiosurgery group. The complications of treatment were similar. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Radiation Therapy, Yale / 30.09.2016

MedicalResearch.com Interview with: Nataniel Lester-Coll, MD Chief Resident in Radiation Oncology at Yale New Haven, Connecticut  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Recurrent Glioblastoma Multiforme (GBM) has limited treatment options and the prognosis is poor. Mibefradil diydrochloride was identified using a high-throughput compound screen for DNA double stranded break repair inhibitors. Mibefradil was found to radiosensitize GBM tumor cells in vitro and in vivo. Based on these findings, we sought to determine the maximum tolerated dose of mibefradil and radiation therapy in a Phase I recurrent GBM study. Eligible patients with recurrent  Glioblastoma Multiforme received Mibefradil over a 17 day period, with hypofractionated radiation (600 cGy x 5 fractions). There are 18 patients currently enrolled who have completed treatment. Thus far, there is no clear evidence of radionecrosis. A final dose level of 200 mg/day was reached as the maximum tolerated dose. The drug was very well tolerated at this dose. We saw intriguing evidence of enhanced local control in selected cases. Patients enrolled in a translational substudy who received Mibefradil prior to surgery were found to have adequate levels of Mibefradil in resected brain tumor tissue. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Case Western, MRI, Radiology, Technology / 19.09.2016

MedicalResearch.com Interview with: Dr. Pallavi Tiwari PhD Assistant Professor biomedical engineering Case Western Reserve University MedicalResearch.com: What is the background for this study? What are the main findings? Response: One of the biggest challenges in neuro-oncology currently is distinguishing radionecrosis, a side-effect of aggressive radiation, from tumor recurrence on imaging. Surgical intervention is the only means of definitive diagnosis, but suffers from considerable morbidity and mortality. The treatments for radionecrosis and cancer recurrence are very different. Early identification of the two conditions can help speed prognosis, therapy, and improve patient outcomes. The purpose of this feasibility study was to evaluate the role of machine learning algorithms along with computer extracted texture features, also known as radiomic features, in distinguishing radionecrosis and tumor recurrence on routine MRI scans (T1w, T2w, FLAIR). The radiomic algorithms were trained on 43 studies from our local collaborating institution - University Hospitals Case Medical Center, and tested on 15 studies at a collaborating institution, University of Texas Southwest Medical Center. We further compared the performance of the radiomic techniques with two expert readers. Our results demonstrated that radiomic features can identify subtle differences in quantitative measurements of tumor heterogeneity on routine MRIs, that are not visually appreciable to human readers. Of the 15 test studies, the radiomics algorithm could identify 12 of 15 correctly, while expert 1 could identify 7 of 15, and expert 2, 8 of 15. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer, Cost of Health Care / 12.08.2016

MedicalResearch.com Interview with: Wuyang Yang, M.D., M.S. Research Fellow Department of Neurosurgery Johns Hopkins Hospital Baltimore, MD 21287 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The treatment for glioblastoma (GBM) patients involves a combined approach of surgery, radiation therapy and chemotherapy. Despite advancement in the therapeutic approaches for GBM, differing socioeconomic status result in disparities in health-care access, and may superimpose a significant impact on survival of glioblastoma patients. Insurance status is an indirect indicator of overall socioeconomic status of a patient, and has been shown to correlate with survival of patients with malignant tumor in other parts of the body. We conducted the first study to determine a relationship between different types of insurance and survival of GBM patients. In our study of 13,665 cases of GBM patients, we found that non-Medicaid insured patients have a significant survival benefit over uninsured and even Medicaid insured patients. This is the first time a study describes this relationship in glioblastoma patients, and also the first to compare and quantify the likelihood of poor prognosis between different insurance categories. A difference in insurance coverage was also uncovered, and patients with insurance were more likely to be older, female, white, and married. In addition, we found that younger, female, married patients with smaller tumor size survive longer than other patients, which confirmed findings in existing literature. (more…)
Abuse and Neglect, Author Interviews, Brain Cancer - Brain Tumors / 06.08.2016

Novocure is the developer of Optune, which uses Tumor Treating Fields to treat cancer. Tumor Treating Fields, or TTFields, are low intensity, alternating electric fields within the intermediate frequency range. TTFields disrupt cell division through physical interactions with key molecules during mitosis. This non-invasive treatment targets solid tumors. MedicalResearch.com: What is the background for this study? What are the main findings? Response: The National Comprehensive Cancer Network (NCCN) has recommended Optune as a standard treatment option for newly diagnosed glioblastoma (GBM) in its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers. NCCN panel members designated Optune together with temozolomide as a category 2A treatment for newly diagnosed GBM for patients with good performance status, indicating uniform consensus among panel members to add Optune to the guidelines for newly diagnosed GBM. Optune has been included in the NCCN Guidelines as a category 2B treatment option for recurrent GBM since 2015. The recommendation follows the publication of Novocure’s EF-14 phase 3 pivotal trial data in The Journal of the American Medical Association (JAMA) in December, 2015. The EF-14 phase 3 pivotal trial demonstrated that adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival in newly diagnosed GBM. Glioblastoma, also called glioblastoma multiforme, or GBM, is a type of primary brain cancer. Approximately 12,500 GBM tumors, or tumors that may transform into GBM, are diagnosed in the U.S. each year. GBM is the most common type of primary brain cancer in adults. It is more likely to appear in older adults and to affect men than women. GBM is one of the deadliest forms of cancer, with patients typically not surviving beyond 15 months after diagnosis. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Pharmacology / 29.06.2016

MedicalResearch.com Interview with: Dr Kieran Breen PhD Director of Research, Brain Tumour Research University of Portsmouth, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is evidence that aspirin (acetyl salicylic acid) can be toxic to brain tumour cells. However, its existing preparations cannot readily enter the brain because the drug is a suspension rather than being completely soluble. Furthermore, there can be significant side effects associated with the existing form of the drug including gastric bleeding. The object of this research was to develop a new formulation of aspirin which is truly soluble. When combined with two other compounds, the drug enters the brain and can therefore target the tumour cells. This study also showed that aspirin can kill tumour cells without causing any damage to the normal nerve cells. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Diabetes / 27.06.2016

MedicalResearch.com Interview with: Dr. Judith Schwartzbaum PhD Associate professor of epidemiology Ohio State's Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? Response: Meningioma is a slow-growing brain tumor that is associated with obesity. To further understand this risk we examined records of blood sugar levels within approximately 15 years before tumor diagnosis comparing blood sugar levels of people who developed meningioma to those in people who did not. MedicalResearch.com:What are the main findings? Response: To our surprise we found that risk of this tumor was lower in people with high levels of blood sugar and diabetes. (more…)
ASCO, Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Immunotherapy / 04.06.2016

MedicalResearch.com Interview with: Wayne L. Furman, MD Department of Oncology Jude Children's Research Hospital Memphis, TN 38105-3678 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Furman: Despite improvement in 2-yr EFS from 46% to 66% with the inclusion of dinutuximab, a monoclonal antibody that recognizes a glycoprotein on neuroblasts called ‘GD2’ (disialoganglioside), more than one-third of children with high-risk neuroblastoma still are not cured. Therefore novel therapeutic approaches are needed for this subset of patients. The clinical evaluation of various anti-GD 2 monoclonal antibodies in children with neuroblastoma has been exclusively focused on treatment of patients after recovery from consolidation, in a state of ‘minimal residual disease’. This is because traditionally chemotherapy has been thought to be too immunosuppressive to combine with monoclonal antibodies. However recent studies suggest, even in the setting of “bulky” solid tumors, the combination of chemotherapy with monoclonal antibodies can enhance the effectiveness of the antibodies. First, chemotherapy can increase the efficacy of antibodies by depleting cells of the immune system that suppress immune function. Also chemotherapy-induced tumor cell death can trigger tumor antigen release, uptake by antigen processing cells and an enhanced antitumor immune response. There is also data that anti-GD2 monoclonal antibodies can suppress tumor cell growth independent of immune system involvement. Furthermore anti-GD2 monoclonal antibodies and chemotherapy have non-overlapping toxicities. All of these reasons were good reasons to evaluate the addition of a novel anti-GD2 monoclonal antibody, called hu14.18K322A, to chemotherapy, outside the setting of minimal residual disease, in children with newly diagnosed children with high-risk neuroblastoma. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, PLoS / 13.05.2016

MedicalResearch.com Interview with: Katarina Truvé PhD Swedish University of Agricultural Sciences and Kerstin Lindblad-Toh Uppsala University MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function. (more…)
Author Interviews, Blood Pressure - Hypertension, Brain Cancer - Brain Tumors / 22.04.2016

MedicalResearch.com Interview with: Hervé Chneiweiss MD PhD Bâtiment A3 pièce 336 Case courrier 2 Plasticité Gliale et Tumeurs cérébrales Neuroscience Paris Seine (directeur) Inserm/Université Pierre et Marie Curie MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Chneiweiss: Treatments available for glioblastoma -- malignant brain tumors -- have little effect. An international collaboration[1] led by the Laboratoire Neurosciences Paris-Seine (CNRS/ INSERM/UPMC)[2] tested active ingredients from existing medications and eventually identified one compound of interest, prazosin, on these tumors. We chose to study the most common malignant tumors that develop from brain cells, glioblastomas, which represent the fourth most frequent cause of cancer deaths among adults and the second in children. This is due to the inefficacy of current treatments. Indeed, a glioblastoma can resist treatment and reawaken from a very small number of tumor cells called glioblastoma-initiating cells (GIC). It is these cells -- whose characteristics and properties resemble those of stem cells -- that were targeted in the study. Rather than trying to discover new compounds, the team opted for repositioning existing drugs. In other words, we tested a collection of substances used for so long to treat other conditions that their patents have now fallen into the public domain[3]. This method makes it possible to develop new active ingredients cheaply and very rapidly. Twelve hundred compounds were thus tested on normal human neural stem cells and on glioblastoma-initiating cells from different aggressive tumors. Twelve of these compounds showed a toxic effect on GIC -- and none on the normal neural stem cells. The most effective was prazosin. Tested in mice carrying glioblastoma-initiating cells, prazosin significantly reduced the size of tumors and prolonged survival of the mice by more than 50%. [1] Including scientists from the Laboratoire d'Innovation Thérapeutique (CNRS/Université de Strasbourg), the Stanford University Institute for Stem Cell Biology and Regenerative Medicine (USA) and the Instituto Estadual do Cérebro Paulo Niemeyer in Rio de Janeiro (Brazil). [2] This laboratory forms part of the Institut de Biologie Paris-Seine. [3] Pharmaceutical compounds are protected by a patent for 20 years after their discovery. Because of the length of the clinical trials that are necessary before a drug can be put on the market, the duration of their patent protection does not normally exceed 10-15 years after a Marketing Authorization (MA) is granted. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Brigham & Women's - Harvard, PNAS / 06.04.2016

MedicalResearch.com Interview with: Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114

MedicalResearch.com: What is glioblastoma and why is it difficult to treat?

Dr. Jain: Glioblastoma (GBM) is the most common malignant tumor of the brain, and remains highly lethal. The standard treatment consists of surgical removal followed by chemo-radiation and anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) antibody. Unfortunately, glioblastoma cells invade the brain far from the original tumor mass. Hence, even with the best surgical techniques it is not possible to remove all tumor cells, as they are embedded in vital parts of the brain at the time of the surgery. As a result, even after multimodal therapies, most  glioblastoma patients succumb to their disease within 2 years. New approaches are desperately needed.

MedicalResearch.com: What is anti-angiogenic therapy and why is it used for glioblastoma?

Dr. Jain: One key feature ofglioblastomas is their highly abnormal, leaky and ineffective vasculature. This leads to brain swelling around the tumor and poor tumor blood perfusion, which in turn can render the tumors more aggressive. These vascular abnormalities are due to the uncontrolled overproduction in GBMs of angiogenic factors such as VEGF. Anti-angiogenic therapies using anti-VEGF agents can transiently “normalize” the GBM vasculature structure and function and reduce brain swelling, increase blood perfusion, and impact morbidity and survival. Unfortunately, even when this therapy is added to the standard therapy with surgery and chemo-radiation, GBM patients typically do not survive on average more than 1.5 years. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, Pediatrics, University of Pennsylvania / 04.02.2016

MedicalResearch.com Interview with: Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia   Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania   Medical Research: What is the background for this study? What are the main findings? Response: This study originates from our long-standing interest in studying pediatric low-grade gliomas (PLGGs), which are the most commonly diagnosed brain tumor in children. While several PLGGs have been found to harbor mutations/gene fusions driving the mitogen-associated protein kinase (MAPK) pathway leading to clinical trials testing MAPK inhibitors, these tumors remain poorly categorized and not enough is known about specific genetic mutations driving different tumor sub-types and the potential for specific targeted therapeutics. Our current study encompasses analysis of the largest combined genomic dataset of pediatric low-grade gliomas samples.  In doing this we, identified the MYB-QKI gene fusion, a non-MAPK related event, as the common genetic event driving a rare PLGG sub-type, called angiocentric gliomas. We have reported a novel tri-partite mechanism by which MYB-QKI mediates its oncogenic effect, this being the first report of a single gene rearrangement utilizing three different paths to cause cancer.
  • First, this gene rearrangement activates MYB, which is a proto-oncogene that is normally not expressed in the developed brain.
  • Second, we found that the rearrangement leads to translocation of QKI-related enhancers close to MYB’s promoters, thereby driving MYB-QKI expression in these tumors. Furthermore, MYB-QKI can also regulate its expression in a positive feedback loop.
  • Third, the tumor suppressor activities of QKI are disrupted in MYB-QKI. Such collaboration of genetic and epigenetic dysregulation in a single genetic rearrangement has previously not been reported.
(more…)
Author Interviews, Brain Cancer - Brain Tumors, Dermatology, JAMA / 27.01.2016

MedicalResearch.com Interview with: Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital University of Copenhagen Hellerup, Denmark   Medical Research: What is the background for this study? What are the main findings? Dr. Egeberg: There appears to be an overlap in the pathogenesis of rosacea and glioma, focused around matrix metalloproteinases. Rosacea may be associated with an increased risk of glioma, however, it is important to note that the absolute risk is still low. Whether this is a causal link is not known. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, JAMA / 16.12.2015

MedicalResearch.com Interview with: Roger Stupp, MD Professor & Chairman Department of Oncology & Cancer Center University of Zurich & University Hospital Zurich (USZ) Zürich / Switzerland Medical Research: What is the background for this study? Dr. Stupp: Tumor Treating Fields are an entirely novel modality in cancer treatment. Over 10 years ago researchers demonstrated that alternating electrical fields will block cell growth, interfere with organelle assembly, in particular perturb the spindle apparatus and cell division, all leading to mitotic arrest and ultimately apoptosis. This was shown in vitro, but importantly also in vivo animal models including not only mice and rats, but also hamsters and rabbits with deep seated solid tumours. So the question was whether we can demonstrate such an effect also in the clinic. Glioblastoma are locally invasive and aggressive tumours in the brain. They usually do not metastasise however they grow diffusely within the CNS and despite the best possible surgery, radiation and chemotherapy virtually always recur. We thus applied alternating electrical fields therapy, so called Tumor Treating Fields to the scalp of patients with newly diagnosed glioblastoma. After the end of standard chemoradiotherapy (TMZ/RT), patients were randomized to receive either standard maintenance TMZ-chemotherapy alone or in combination with TTFields. Almost 700 patients were randomized, here we report on a preplanned interim analysis looking at the first 315 patients included once they were followed for at least 18 months. The data on the first 315 patients are mature and allowed the IDMC to conclude that the trial should be stopped and the results made available. Medical Research: What are the main findings? Dr. Stupp: The study demonstrated a consistent prolongation of both progression-free and also of overall survival for patients who have been treated with TTFields in addition to standard therapy. The median progression-free survival and overall survival were prolonged by 3 months, translating to an absolute increase in overall survival at 2 years of 14%, from 29% to 43%. Or a hazard ratio of 0.74 for overall survival and of 0.62 for progression-free survival. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research / 02.09.2015

Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C. Medicalresearch.com Interview with: Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C.   MedicalResearch: What is the background for this study? What are the main findings? Dr. Packer: The background is that medulloblastoma is the most common childhood malignant brain tumor. It carries with it a variable prognosis. For some subsets of patients, with current available treatment which includes surgery, radiation and chemotherapy, we see survival rates as high as 90% (and often cures) 5 years following diagnosis and treatment. However, for some subsets of patients, survival rates are much poorer, in those with higher risk characteristics as low as 40% at 5 years. Current treatment also carries with it a significant risk for long term sequelae, including intellectual loss secondary to radiation therapy and persistent, at times devastating neurologic complications such as unsteadiness. To try to improve our understanding and ultimately our therapy for medulloblastoma, an international working group has shared patient specimens and patient information to attempt to determine what the molecular predictors of outcome are for children with medulloblastoma and if such molecular genetic findings can be used to develop better, safer therapies. Children’s National is part of this international collective of institutions, which published this and other studies. The main findings of this study are that complex, integrated genetic analysis of tumor specimens can be used to better understand and set the scene for better treatment of medulloblastoma.  Medulloblastoma can be broken into relatively distinct, molecular subtypes each with its own prognosis and potential therapy. A major finding of this study was that within a given tumor, different areas showed the same molecular genetic pattern. The importance of this is that since the tumors are relatively the same in different areas, molecularly-targeted therapies have an excellent chance of working on the entire tumor, resulting in better tumor control and safer treatments. (more…)
Author Interviews, Biomarkers, Brain Cancer - Brain Tumors, Chemotherapy, Neurology, Radiation Therapy / 20.08.2015

Jorg Dietrich, MBA MMSc MD PhD Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical SchoolMedicalResearch.com Interview with: Jorg Dietrich, MBA MMSc MD PhD  Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Dietrich: Understanding the adverse effects associated with cancer therapy is an important issue in oncology. Specifically, management of acute and delayed neurotoxicity of chemotherapy and radiation in brain cancer patients has been challenging. There is an unmet clinical need to better characterize the effects of standard cancer therapy on the normal brain and to identify patients at risk of developing neurotoxicity. In this regard, identifying novel biomarkers of neurotoxicity is essential to develop strategies to protect the brain and promote repair of treatment-induced damage. In this study, we demonstrate that standard chemotherapy and radiation in patients treated for glioblastoma is associated with progressive brain volume loss and damage to gray matter – the area of the brain that contains most neurons. A cohort of 14 patients underwent sequential magnetic resonance imaging studies prior to, during and following standard chemoradiation to characterize the pattern of structural changes that occur as a consequence of treatment. (more…)
Author Interviews, Brain Cancer - Brain Tumors / 05.05.2014

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. (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 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. (more…)