Understand why deadly brain cancer comes back

The deadliest form of brain cancer comes back because tumors adapt to treatment by recruiting help from nearby healthy tissue, say researchers who are trying to find a cure for the disease.

A new study, conducted by a global team including specialists from the University of Leeds, has found that ‘in response to treatment, high-grade gliomas appear to reshape the surrounding brain environment, potentially creating interactions with nearby neurons and immune cells in ways that protect tumor cells. and hide them from the body’s defenses.

The team also discovered that lower grade tumors often develop a new mutation that allows cells to start dividing more quickly, potentially catapulting them into a higher quality form.

Glioma brain tumors are rare, but a diagnosis is devastating as there is currently no cure. Low-grade gliomas have a better survival rate than, but often progress to high-grade gliomas. More than 90% of people with high-grade tumors die within five years.

Current treatments include surgery , radiotherapy and chemotherapy. The results indicate that new drugs are needed to complement them.

Dr Lucy Stead, Associate Professor of Brain Cancer Biology at the University of Leeds Medical School and lead UK academic on the study, said: “The brain is an extremely complex organ made up of many different kinds of cells, and brain tumors are just as diverse and complicated.

“Learning from the tissues of the affected individual is the best way to cure the disease of the individual. This study, which required a worldwide effort to acquire enough glioma samples to adequately feed it, gave us unprecedented insight into the progression of these deadly tumors and the ways that we might finally be able to stop them.”

Sue, a patient with a brain tumor of York, died in September 2017 after a seven-year battle with illness. Her husband of 50 years, Geoff, is now an ambassador for Yorkshire’s Mind Tumor Charity, attending events to help raise money for research and awareness of the most brain cancers.

Welcoming the findings, he said: “Sue fought bravely and without a single word of complaint or self-pity for 7 year. He’s my driver. The types and positions of the tumors make them a difficult problem to “solve”. It is a scandal that the survival rate for brain tumors is not better today than it was years ago.

“In my experience, it seems that a one of a kind approach is being applied to treatment at the moment and any form of treatment that specifically targets the person should be an improvement.

“The fact that research is undertaken also has a beneficial effect for people and their families. This generates hope.”

Researchers are studying why gliomas progress to a higher-grade form, and why they survive and continue to grow after treatment.

They collected multiple glioma samples over time, when switching from low to high quality, and before and after treatment. They then looked at how cells change and adapt to see if they could find ways to stop them, using new drugs.

Mutation and Cell Interactions So Far These unknowns could now be targeted with new drugs that prevent tumor cells from progressing and adapting to treatment. In this way, the study has opened up new avenues of research that may lead to more effective drugs to be offered to patients.

The research was led by Full Professor of the Jackson Laboratory (JAX) Florine Deschenes Roux Chair and lead author, Dr. Roel Verhaak, and Dr. Frederick Varn, postdoctoral associate and first author of Jane Coffins Childs.

The Dr Varn said: “By analyzing genetic and transcriptional data from this large cohort of patients, we are beginning to understand how tumors evolve to adapt to normal therapy.

“This study clearly showed that not all tumors change in the same way. Knowing this, we can develop therapies that are better suited to each patient’s disease in the future.”

Dr Verhaak said: “The GLASS project has gained tremendous momentum and just getting started.

“We are on track to triple our patient cohort and datasets. We are on the verge of comprehensively dissecting the resistance process and making significant progress towards better outcomes for people with glioma.

The involvement of the University of Leeds in this worldwide consortium is partly due to the presence of the Leeds Neuropathology Investigate Tissue Lender, which is co-funded by Yorkshire’s Mind Tumor Charity and OSCAR’s Pediatric Brain Tumor Charity.

Marie Peacock, CEO of Yorkshire’s Mind Tumor Charity, said: “We are delighted to co-fund the Leeds Neuropathology Analysis Tissue Bank, ensuring that we have the research infrastructure to undertake research right here in the Yorkshire to find new treatments and ultimately a cure for brain tumours.”

Marie Hughes, who established OSCARs Pediatric Brain Tumor Charity after the death of her son a brain tumor in 2014, and whose husband and another son died of a brain tumor within the past two years, said: “Supporting the work of The Tissue Bank is so Gliomas are the most common brain tumor in children and research conducted because of the presence in Leeds of this important research resource is essential to adapting treatments to be less devastating and more effective, and to improving outcomes in life.

“This is an extremely exciting project to be involved in, because the impact it will have on brain tumor research, not just in Yorkshire, but nationally and globally, is huge.”

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