The Subventricular Zone, Bevacizumab and an opportunity in Plymouth – Brain Tumour Research

Cases of successful treatment in Glioblastoma (GBM) offer hope that an enhanced understanding of the pathology will improve the prognosis. The cell of origin in GBM remains controversial. Recent evidence has implicated stem cells as cells of origin in many cancers. Neural stem/precursor cells (NSCs) are being evaluated as potential initiators of Glioblastoma (GBM) tumorigenesis. The NSCs in the subventricular zone (SVZ) have demonstrated similar molecular profiles and share several distinctive characteristics to proliferative glioblastoma stem cells (GSCs) in GBM. Genomic and proteomic studies comparing the SVZ and GBM support the hypothesis that the tumour cells and SVZ cells are related. Additionally, key genetic mutations in GBM for the most part carry regulatory roles in the SVZ as well. This article comprehensively discusses and reviews the role of the Subventricular Zone in Glioblastoma: Genesis, Maintenance, and Modelling

Bevacizumab has US approval for treatment of recurrent GBM, but survival benefits with monotherapy are modest. Based on preclinical and early clinical data indicating that CD105 upregulation may represent a mechanism of resistance to bevacizumab, this study hypothesised that combining bevacizumab with the anti-CD105 antibody TRC105 may improve efficacy in recurrent GBM but unfortunately, although bevacizumab was well tolerated in patients with recurrent GBM, no difference in efficacy was observed compared to bevacizumab monotherapy.

The brain is composed of billions of neuronsvulnerable cells that require a protective environment to function properly. This delicate environment is protected by 400 miles of specialized vasculature designed to limit which substances come into contact with the brain. This blood-brain barrier is essential for protecting the organ from toxins and pathogens. But in the context of neurological disease, the barrier also blocks the passage of therapeutic drugs. For years, it has been the goal of neuroscientists and vascular biologists alike to find the magic bullet for temporarily opening and resealing the barrier for drug administration. Now a team of Yale researchers have developed an antibody as a tool for unlocking the blood-brain barrier for a couple of hours at a time, allowing for the delivery of drugs to a diseased brain. The team published its findings in Nature Communications on 4th March.

Despite advances in neurosurgery, chemotherapy and radiotherapy, GBM remains one of the most treatment-resistant CNS malignancies, and the tumour inevitably recurs. The majority of recurrences appear in or near the resection cavity, usually within the area that received the highest dose of radiation. Many new therapies focus on combatting these local recurrences by implementing treatments directly in or near the tumour bed. This review, discusses the latest developments in local therapy for glioblastoma, focusing on recent preclinical and clinical trials. The approaches discussed include novel intraoperative techniques, various treatments of the surgical cavity, stereotactic injections directly into the tumour, and new developments in convection-enhanced delivery and intra-arterial treatments

Clumps (called plaques) of the protein amyloid beta are found throughout the brains of people who develop the cognitive symptoms of Alzheimers. Results from a new study by NCI-funded researchers, published in Cancer Discovery, suggest that amyloid beta also plays a role in the spread (metastasis) of melanoma to the brain. The researchers found that melanoma cells that travel to the brain produce their own supply of amyloid beta and that this protein is necessary for their survival. They also showed how amyloid beta achieves this feat: by damping down the bodys normal immune response against cancer cells that make it into the brain. In fending off the immune response, the protein buys the cancer cells time to grow into full-fledged tumours.

Finally, this week there is a call for a funded PhD project that will be carried out in collaboration with the Plymouth Centre of Excellence for Brain Tumour Research which has a biobank of brain tumour samples and associated data, including genomic and MRI data. This interdisciplinary project brings together clinical expertise in brain tumour and neuro-imaging and expertise in AI, software development, and biomedical data analysis. The aim of the project is to build an AI-based tool for clinicians to use to assess brain tumours to help with treatment planning and to inform clinical decision-making. This will have a significant impact on patient treatment outcome (e.g. a reduction in the number of unnecessary invasive procedures). The project will use machine learning to correlate radiomic, radiological and histological findings in meningiomas, bench marked against the gold standard, highly predictive genomic data from meningioma tissue, in order to develop better non-invasive predictive models of tumour grade and clinical outcome. Such models would help with clinical decisions about surveillance and surveillance intervals vs surgery +/- radiotherapy. This is a Funded PhD Project (UK Students Only) at the University of Plymouth and is an Assessment of Brain Tumours Using Machine Learning and MRI Radiomics, where the ideal candidate should have a strong background in computer science, data science, engineering or mathematics.

The Subventricular Zone, Bevacizumab and an opportunity in Plymouth – Brain Tumour Research

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