Results published in
Frontiers in Oncology from the
Phase 3 EF14 clinical trial assessing the efficacy and safety of TTFields combined with maintenance temozolomide show significantly improved progression free survival (PFS) and overall survival (OS) in elderly patients with newly diagnosed glioblastoma
, without significant increases in systemic toxicity or negatively affecting patient health-related quality of life (HRqol).
How glioma cells handle stress
A study published in
Nature Genetics has described how brain tumours adapt to biological stresses put upon them and become more aggressive when glioblastoma cells are exposed to low oxygen states and irradiation. Through observation of DNA methylation patterns (a process that turns genes 'on' or 'off'), the researchers discovered how these tumour cells become more resilient to these stresses by changing which genes they express in response. It is hoped the results provide information which could lead to more effective treatments for brain tumours.
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Research reveals new insights into how glioblastoma develops
A paper in
Nature Communications authored by a team of scientists at Queen Mary University of London (UK) provides new insights into how glioblastoma tumours develop, potentially identifying new targets for individualised treatments.
Using powerful lab techniques to track changes in the function of genes that occur in the disease, the team identified significant molecular alterations in human cells which could be targeted to develop new treatments and predict a patient’s response to drugs. Read more
here and
here.
New immunotherapy study for glioblastoma
A
clinical trial run by the National Cancer Institute (NCI), National Institutes of Health (NIH) in the United States is testing a new immunotherapy treatment to improve survival in patients with glioblastoma or gliosarcoma. Cancer cells often use 'checkpoint proteins' to suppress the immune system and avoid being attacked. Immune Checkpoint Inhibition (ICI) allows drugs that block checkpoint proteins to enable T-cells to better kill tumour cells. The trial aims to find out whether patients with newly diagnosed disease who receive immune checkpoint inhibitors alongside the standard of care develop an immune response in the blood, and if that results in improved outcomes compared to those without a response. The trial also aims to evaluate a test to help determine who is likely to respond to the treatment.
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Study highlights the use of nanoparticles to improve drug delivery of temozolomide across the blood brain barrier
A new study in the
European Journal of Pharmaceutics and Biopharmaceutics reports a novel method of delivering temozolomide across the blood brain barrier to target glioblastoma and brain cancer stem cells. Temozolomide acid (TMZA) was loaded into human serum albumin nanoparticles (HAS NPs) to discover optimal conditions for effective delivery while retaining stability and then to assess cellular uptake in glioblastoma cell lines post incubation. Results revealed that the optimised nanoparticle formula showed high toxicity for GBM cells with an excellent cellular uptake of the temozolomide acid of 50-100%.
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Adding carboplatin during radiotherapy improves survival in high-risk medulloblastoma, according to research results
Published in
JAMA Ocology are findings from a
randomised clinical trial of medulloblastoma patients aged 3 to 21 years of age defined as ‘high risk’, who were treated with a standard protocol of chemoradiation including weekly vincristine chemotherapy with or without daily carboplatin, followed by six cycles of maintenance chemotherapy with or without 12 cycles of a drug called isotretinoin. The research team concluded that: “...therapy intensification with carboplatin improved event-free survival by 19% at 5 years for children with high-risk group 3 medulloblastoma. These findings further support the value of an integrated clinical and molecular risk stratification for medulloblastoma.”
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Advanced technique offers new insights about the dynamics of gliomas
A paper in
Nature Genetics describes how researchers have used advanced 'bioinformatic' techniques to make new discoveries about the growth and behaviour of glioma brain tumours, effectively mapping distinct tumour cell behaviours in gliomas and identifying key chemical and genetic programming marks that shift gliomas to more aggressive states. One key characteristic noted using the specialised ‘single cell multi-omics’ approach was to identify the very plastic nature of the cellular architecture of IDH-wildtype glioblastoma (IDH status is an important prognostic indicator for patients with high grade glioma, 'wildtype' being the unmutated form), highlighting that this is a key factor in how IDH-wildtype glioblastoma can survive stem-cell killing treatments by regenerating cells from its pool of mature cells.
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Newly developed gel enhances the effectiveness of CAR-T immunotherapy in a mouse model of glioblastoma
A lab-based investigation in
Science Advances has reported that CAR-T immunotherapy administered into the surgical cavity following partial glioblastoma removal is more effective when delivered with a newly developed fibrin gel. The research, carried out in a mouse model, explains how the gel aids CAR-T cell distribution in the brain by acclimating the T cells to the post-surgical wound environment, while simultaneously preventing the tumour from recovering.
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A common diabetes drug shows promise against rare childhood brain tumour (ependymoma) in laboratory studies
A study published in
Science Translational Medicine has investigated whether the anti-diabetic drug metformin could improve survival for paediatric patients with ependymoma brain tumours by inhibiting a protein that is overexpressed in a subset of patients with the disease. Children with posterior fossa group A (PFA) ependymomas overexpress a protein called EZHIP (EZH inhibitory protein), which enhances metabolic pathways involving glucose metabolism. In a rodent model, metformin was able to lower EZHIP concentrations and suppress pathways involving glucose metabolism which, the researchers report, resulted in decreased tumour volume and increased survival.
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Postoperative speech impairment and surgical approach to posterior fossa tumours in children: a prospective European multicentre cohort study
An observational study across 26 treatment centres in nine European countries has found that children under 18 years of age undergoing surgery for posterior fossa brain tumours had various factors that influenced speech impairment. The study results, published in
The Lancet Child & Adolescent Health found that midline tumour location, younger age, and high-grade tumour histology were all found to increase the risk of speech impairment following surgery. The study authors explain that: “The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI [post-operative speech impairment]. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors.”
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Largest international study of rare childhood brain cancer shows early molecular diagnosis and aggressive therapy could improve patient outcomes
A large-scale study published in
The Lancet Child & Adolescent Health sheds light on how to more effectively treat EMTRs (Embryonal Tumour with Multi-layered Rosettes), a rare and aggressive paediatric brain tumour first identified 21 years ago. In the largest study of its kind for this tumour type, 140 international collaborators analysed over 200 tumour samples of primary EMTRs through the
Rare Brain Tumour Consortium. The paper goes into detail on the genetic profiles, disease patterns and clinical features of ETMRs. Following a systematic review of treatments received by patients, the data suggests that the considerable number of ETMR patients could potentially benefit from a treatment protocol that combines surgery, chemotherapy, and some radiation.
The study’s second author Dr Palma Solano-Paez said: “Not only do our findings have immediate implications for children around the world who may have an ETMR, the data could help support the development of clinical trials and more targeted therapies for these rare cancers.”
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Weighing cancer cells to personalize drug choices
Published in
Cell Reports, a retrospective study by researchers at MIT and Dana-Farber Cancer Institute in the US details a novel technique for assessing the drug susceptibility of individual patients' glioblstoma tumours by detecting subtle changes in the mass of tumour cells in response to different treatments. The procedure involves exposing cancer cells from a patient that have been grown in the lab to a drug and then measuring any changes in mass. Treatment response may match patients with the most effective therapies for their tumour, which the researchers report could be especially useful for cancers lacking genomic biomarkers (which act as indicators for response to treatment and help to predict prognosis). Researchers tested the validity of the mass measurement approach by measuring the response of temozolomide in samples derived from 69 patients with glioblastoma paired with genomic data.
Overall findings concluded that cell mass is a valid, promising indicator of treatment response for cancers and drugs that lack genomic biomarkers. Read more
here and
here.
