Treatments:
Global Coalition for Adaptive Research and Polaris Group Announce Commencement of ADI-PEG 20 in GBM AGILE Trial ADI-PEG20 has been added to the list of potential treatments for patients in the GBM AGILE trial taking place in Europe, the U.S, Canada and Australia. Arginine is an amino acid that is essential for protein synthesis and survival of cells. Some cancer cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 is designed to deplete the external supply of arginine, which causes arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed.
Our Centre of Excellence at Imperial College London is also working with the Polaris Group investigating ADI-PEG20 for GBM treatment. In the project named WISTERIAN, the research team are developing the protocol for a window of opportunity trial, where ADI-PEG20 is administered preoperatively alongside radiotherapy for newly diagnosed GBM patients. Find out more here.
Research:
The DRD2 Antagonist Haloperidol Mediates Autophagy-Induced Ferroptosis to Increase Temozolomide Sensitivity by Promoting Endoplasmic Reticulum Stress in Glioblastoma. Temozolomide resistance remains a major obstacle in the treatment of glioblastoma. The combination of temozolomide with another agent could offer an improved treatment option if it could overcome chemoresistance and prevent side effects. This study, published in Clinical Cancer Research, provides experimental evidence for repurposing haloperidol as an adjunct therapy to inhibit adaptive temozolomide resistance to enhance the efficacy of chemoradiotherapy in glioblastoma, a strategy that may have broad prospects for clinical application.
New Method Identifies Constrained Noncoding Mutations as Potential Drivers of Medulloblastoma Researchers have developed a new method to identify noncoding mutations (changes in DNA that are not genes) that may play a driving role in paediatric medulloblastoma. Published in PNAS, the study also linked identified noncoding constraint mutations (NCCMs) with changes to how cancer cells respond to one type of cancer therapy. The researchers suggest that their findings could lead to better diagnostics and more personalised treatments.
Inhibition of hyaluronic acid degradation pathway suppresses glioma progression by inducing apoptosis and cell cycle arrest Abnormal hyaluronic acid (HA) metabolism is a major factor in tumour progression. Metabolic regulation of HA mainly includes HA production and breakdown. Published in Cancer Cell International, this study demonstrated that Hyaluronidase 2 (an enzyme that breaks HA down) is abnormally overexpressed in glioma. Moreover, they found that HYAL2 overexpression is associated with multiple glioma clinical traits and acts as a key indicator for glioma prognosis. Targeting HYAL2 could inhibit glioma progression by inducing glioma cell apoptosis and cell cycle arrest.
Interesting read:
Not specifically brain tumour focused, but an interesting read nonetheless, this news feature published in Nature last week discusses the FDA accelerated drug approval system. It highlights the potential pitfalls of not having a sufficient communication system for the removal of drugs that have gone on to be proven ineffective or harmful.
Opportunities:
Brain tumour clinical research needs top-level patient and public involvement to ensure patient needs are in the DNA of the trial or study. You can bring patients closer to your research by using brainstrust's PRIME service, which bridges the gap between the patient community and the clinical community. More information here.