By using a combinational therapeutic strategy, a research team have created a promising approach to combat chemoresistance in GBM.  Glioblastoma often resists front-line chemotherapies, including temozolomide, a drug that damages DNA and triggers tumour cell death. Nearly half of glioblastoma patients resist the treatment by producing a DNA-repairing enzyme, MGMT, but until recently it wasn’t clear why temozolomide wasn’t working for patients who lacked the MGMT enzyme.

Using glioblastoma cell lines and primary glioblastoma cells derived from patient tumour specimens the team discovered that inhibiting two specific proteins when combined with temozolomide, produced an effective “triple combinational therapy” that overcame chemoresistance.

The findings from this three-pronged approach to treating glioblastoma are published this week in Oncogenesis.

In the research update two weeks ago we linked to Dr Fred Gentili telling his story of a brain tumour surgeon becoming a brain tumour patient and I am very sorry to report that Dr Gentili died on Saturday – our condolences to his family friends and colleagues. He is remembered here and this quote from his telling, "The solution to my problem is not going to be surgery, it's going to be research, funding, molecular biology, looking under the microscope to check the cells. The way we're going to solve this problem is by studying it, by researching it."

Researchers at the University of Michigan have discovered how a gene mutation in gliomas leads to cell cycle dysregulation and heightened sensitivity to a class of inhibitors. These findings, recently published in  Cell Reports, present possibilities for more effective therapies for glioma patients with this gene mutation.

UK researchers have identified distinctive biomarkers within patient blood samples, which could signal the presence of glioblastoma. The biomarkers (biological signatures for a disease) were identified within extracellular vesicles – small particles which all cells secrete which carry different information, such as DNA or proteins. The ability to identify these biomarkers within the extracellular vesicles suggests that a liquid biopsy approach could be a viable option for glioblastoma diagnosis, providing both a quicker and less invasive alternative to current diagnostic methods. This work, from researchers at the University of Sussex, was published in the journal Biomedicines. 

Work by researchers based at universities in Glasgow and Manchester have been exploring how to reduce the toxicity patients with glioblastoma experience following treatment with radiotherapy. They propose that drugs called PARP inhibitors could reduce radiation-induced neuroinflammation and reduce the severity of radiation-induced cognitive dysfunction in glioblastoma while at the same time improving tumour control by enhancing radiosensitivity. By targeting the enzyme, PARP, which is involved in the repair of DNA, they propose that suppressing the DNA damage response may also reduce subsequent neuroinflammation. These results are published in the journal Neuro-Oncology Advances.

Although these updates are mainly received via email by researchers and clinicians, they are also used on our website and social media and judging from the feedback we get they are enthusiastically read. Consequently, the tone is hopefully one that will admit those with a keen interest in brain tumour science but perhaps without a professional background. This keen interest is usually caused by being flung into the brain tumour world, as a patient, friend, or family member. We meet many ‘unplanned’ members of the brain tumour community on the lab tours of our research centres, and we are looking forward to re-introducing these opportunities for supporters to meet scientists. I know from the researcher perspective our community arrive armed with knowledge, sophistication around the research into the disease area and many questions of varying complexity, the answering of which is both a challenge and an inspiration.

This week though there are several papers published that for me to produce a pithy overview that would be easily accessible to all who read these updates would prove time consuming in the extreme. Consequently, the titles are reproduced faithfully below with hyperlinks to the articles. From the titles you will be easily able to assess if a click through will provide a benefit.

IMMU-13. Dual IGF1R/IR inhibitor in combination with GD2-CAR T cells as a potent therapeutic strategy for H3K27M-mutant diffuse midline gliomas

IDH Mutated Gliomas Promote Epileptogenesis through D-2-Hydroxyglutarate Dependent mTOR Hyperactivation

Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

Cancer cell heterogeneity and plasticity: A paradigm shift in glioblastoma

Related Reading:

• Chemotherapy for brain tumours
• A 360° virtual lab tour of our University of Plymouth Centre of Excellence

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