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Learn why deadly brain cancer is making a comeback

To summarize: In response to treatment, high-grade gliomas reshape the surrounding brain environment, interacting with nearby neurons and immune cells to protect tumor cells and protect them from the body’s natural defenses.

resource: University of Leeds

Researchers trying to find a cure for the disease say the deadliest form of brain cancer reappears as tumors adapt to treatment by seeking help from nearby healthy tissue.

High-grade gliomas appear to reshape the surrounding brain environment in response to treatment, potentially interacting with nearby neurons in a way that protects tumor cells, a new study by a global team including experts from the University of Leeds has found. Interacts with immune cells and hides them from the body’s defenses.

The team also found that low-grade tumors often develop new mutations that cause cells to start dividing more quickly, potentially catapulting them into higher-grade forms.

Glioma brain tumors are rare, but the diagnosis is devastating because there is currently no cure. Low-grade gliomas have better survival rates than high-grade gliomas, but usually progress to high-grade gliomas. More than 90% of patients with high-grade tumors die within five years.

Current treatments include surgery, radiation therapy and chemotherapy. The findings suggest that new drugs are needed to complement these.

Dr Lucy Stead, Associate Professor of Brain Cancer Biology at the University of Leeds School of Medicine and lead UK scholar on the study, said: “The brain is a very complex organ, made up of many different types of cells, just as diverse and complex as brain tumors.”

“Learning from patient tissue is the best way to cure a patient’s disease. This research requires a global effort to obtain enough glioma samples to fully power it, giving us unprecedented insights into how these deadly tumors progress. , and how we can finally stop them.”

Su, a brain tumor patient from York, died in September 2017 after a seven-year battle with the disease. Her husband of 50 years, Jeff, is now an ambassador for the Yorkshire Brain Tumour Charity, taking part in a drive to raise funds for brain cancer research and advocacy.

Welcoming the findings, he said: “Su fought bravely for seven years without a single complaint or self-pity. This was my driver. The type and location of the tumor made it difficult to really ‘solve’ this. But now the brain Tumor survival rates are not higher than they were 40 years ago, which is a real scandal.”

“In my experience, there seems to be a one-size-fits-all approach to treatment, and any form of targeted therapy specifically for that person has to be an improvement.”

“The fact that research is underway also has a beneficial effect on patients and their families. It offers hope.”

Researchers are investigating why gliomas develop into higher-grade forms, and why they survive and continue to grow after treatment.

Over time, they collected multiple glioma samples that transitioned from low-grade to high-grade, as well as before and after treatment. They then looked at how the cells changed and adapted to see if they could find a way to stop them, using new drugs.

The team also found that low-grade tumors often develop new mutations that cause cells to start dividing more quickly, potentially catapulting them into higher-grade forms.Image is in the public domain

Mutations and previously unknown cellular interactions can now be targeted with new drugs that prevent tumor cells from progressing and adapting to treatment. In this way, the study opens up new avenues of research that may lead to more effective drugs to serve patients.

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

“By analyzing genetic and transcriptional data from this large cohort of patients, we are beginning to understand how tumors change to accommodate standard-of-care treatments,” Dr. Varn said.

“This study clearly shows that not every tumor changes in the same way. Knowing this will allow us to develop treatments that are better suited to each patient’s disease in the future.”

“The GLASS project has built tremendous momentum and is only just getting started,” Dr Verhaak said.

see also

This shows the study's brain scans

“We are tripling our patient cohort and dataset. We are poised to fully dissect the process of drug resistance and make important strides in delivering better outcomes for glioma patients.”

About this Brain Cancer Research News

author: News office
resource: University of Leeds
touch: Press Office – University of Leeds
picture: Image is in the public domain

Original research: closed access.
“Glioma progression is shaped by the interaction of genetic evolution and microenvironment” by Frederick S. Varn et al. cell


Glioma progression is shaped by the interaction of genetic evolution and microenvironment


  • Longitudinal glioma evolution follows an IDH mutation-dependent trajectory
  • hypermutation and CDKN2A Deletion underlies increased proliferation at relapse
  • Recurrent IDH-wild-type tumor cells upregulate neuronal signaling programs
  • Mesenchymal transitions are associated with distinct myeloid cell interactions


The factors that contribute to treatment resistance in diffuse gliomas remain poorly understood. To identify treatment-related cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from temporally isolated tumor pairs from 304 adult patients with isocitrate dehydrogenase (IDH) wild-type and IDH-mutant gliomas.

Tumors recur in different ways, depending on IDH mutation status and due to changes in the composition of histological features, somatic alterations, and microenvironment interactions.Hypermutation and Acquired CDKN2A The deletion was associated with an increase in proliferating tumor cells at recurrence in both glioma subtypes, reflecting active tumor growth.

IDH-wild-type tumors were more aggressive at recurrence, and their tumor cells exhibited increased expression of neuronal signaling programs, reflecting a possible role of neuronal interactions in promoting glioma progression. Mesenchymal transition is associated with the presence of a myeloid cellular state defined by specific ligand-receptor interactions with tumor cells.

Collectively, these relapse-related phenotypes represent potential targets for altering disease progression.

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