Research:
HDAC1 and HDAC6 are essential for driving growth in IDH1 mutant glioma Histone deacetylase inhibitors are promising anti-cancer agents and have already been used in clinical trials. However, a clear understanding of their mechanism or gene targets is lacking, including in low- and high-grade glioma tumours. In this study, the authors genetically analysed patient derived IDH1 mutant cell cultures to work out which HDAC enzymes drive growth in IDH1 mutant gliomas. This study, published in Scientific Reports, identifies HDAC1 and HDAC6 as important and drug-targetable enzymes that are necessary for growth and invasiveness in IDH1 mutant gliomas.
Early clonal extinction in glioblastoma progression revealed by genetic barcoding Glioblastoma progression in its early stages remains poorly understood. Researchers in this study transferred PDGFB and genetic barcodes in mouse brain to initiate gliomagenesis and enable direct tracing of glioblastoma evolution from its earliest possible stage. The findings provide insights into glioblastoma evolution that are inaccessible using conventional retrospective approaches, highlighting the potential of combining clonal tracing and transcriptomic analyses in this field.
A co-author on this study was Sara Lucchini who is now working in the lab of Professor Silvia Marino at The Brain Tumour Research Centre at Queen Mary University of London (QMUL). We asked her about her career so far and she told us “Working on brain tumours for three years while I was a student in Italy, made me realise how little we still know about glioblastoma and how crucial it is to invest more in researching its underpinning biology to, one day, find a cure. The way this tumour develops, resembling some aspects of normal neurodevelopment, is scientifically intriguing and for these reasons, I have decided that I wanted to keep doing my part in this field.”
“In Malatesta’s lab I was able to develop several laboratory skills, which allowed me to secure a PhD position in the Brain Tumour Research Centre of Excellence led by Prof. Silvia Marino. Within this role I am currently working on the development of glioblastoma recurrence model aimed to find a better therapeutic approach for relapsing patients.”
Capturing the Brain Tumor Microenvironment with Tissue Engineering A researcher at Virginia Tech has created a model of the human glioblastoma tumour microenvironment (TME) that incorporates patient derived GBM stem cells, human astrocytes and microglia, and a biophysical force involved in tumourigenesis called interstitial fluid flow. Published in npj Precision Oncology, the model provides a holistic approach to assess the influence of the GBM TME and compare in vitro drug responses with in vivo survival.
Crafting Targeted Treatments in Pediatric Low-Grade Glioma Improves Results The use of targeted therapies focusing on protein pathways in patients with paediatric low-grade gliomas (pLGG) has resulted in several impactful treatments and ongoing trials that have shown effectiveness and tolerability in a real-world setting. According to recent research reported on in Targeted Oncology most of these cases are driven by gene alterations within the MAPK/ mTOR pathways, and molecular diagnostics and new targeted therapies have led to positive outcomes in these patients.
From Australia comes news that Telix Pharmaceuticals Limited has a First Patient Dosed in IPAX-2 Study of TLX101 Brain Cancer Therapy Candidate in Patients with Newly Diagnosed Glioblastoma. IPAX-2 is a Phase I dose escalation study to confirm safety profile of TLX101 in combination with external beam radiation therapy (EBRT) and temozolomide in front-line glioblastoma. Twelve patients are expected to be recruited to evaluate whether the observed safety and drug interaction profile remains suitable in this setting before progressing to a proof-of-concept Phase II study. IPAX-2 is being conducted at six sites across Australia, New Zealand and Europe.
Targeted Drug Combo May Change Care for Rare Brain Tumour Craniopharyngioma. Results from a small clinical trial could offer hope of an effective new option for treatment for papillary craniopharyngioma patients according to a study published in New England Journal of Medicine
Paediatric Brain Cancer Trial Explores Focused Ultrasound and Liquid Biopsy Researchers at Columbia University have begun a clinical trial to assess the safety and feasibility of using focused ultrasound to facilitate the delivery of chemotherapy to progressive diffuse intrinsic pontine gliomas (DIPGs). In this trial, up to 10 participants with DIPGs will receive an oral chemotherapy drug called etoposide before undergoing the focused ultrasound procedure to noninvasively open the BBB at one or two tumour sites. Researchers hope that the focused ultrasound will enable the chemotherapy to penetrate the tumour tissue in higher concentrations. Successful opening and closing of the BBB will be monitored by MRI. The study uses a novel, single-element focused ultrasound transducer under neuronavigational guidance that was designed and tested at Columbia.
In work described as “using the body's 'invisible scalpel' to remove brain cancer,” scientists at the Salk Institute have discovered that anti-CTLA-4 immunotherapy extended the lives of mice with glioblastoma by causing specialised CD4+ T immune cells to 1) infiltrate the brain and 2) tell brain-resident immune cells called microglia to destroy tumour cells. Published in Immunity the findings show the benefit of harnessing the body's own immune cells to fight brain cancer and could lead to more effective immunotherapies for treating brain cancer in humans.
Events:
Featuring sessions on topics such as AI and machine learning in drug discovery, ‘omics and novel target approaches the CRUK Children’s Brain Tumour Centre of Excellence International Summer School 2024 will be focused on “Envisaging the future of children’s brain tumour research in the digital age”.