Understanding Why Deadly Brain Cancer Comes Back

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Overview: In response to treatment, high-grade gliomas remodel the surrounding brain environment and create interactions with nearby neurons and immune cells in ways that protect tumor cells from the body’s natural defenses.

Source: University of Leeds

The deadliest form of brain cancer is making a comeback as tumors adapt to treatment by recruiting help from nearby healthy tissue, say researchers trying to find a cure for the disease.

A new study conducted by a global team including experts from the University of Leeds has found that in response to treatment, high-grade gliomas appear to remodel 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 found that lower grade tumors often develop a new mutation that allows the cells to divide more quickly, potentially catapulting them into a higher form.

Glioma brain tumors are rare, but a diagnosis is devastating because there is currently no cure. Low-grade gliomas have a better chance of survival than, but often develop into 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 indicate 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 the lead British academic for the study, says “the brain is a hugely complex organ made up of many different types of cells, and brain tumors are equally diverse. and complicated.”

“Learning from patient tissue is the best way to cure the patient’s disease. This study, which required a global effort to obtain enough glioma samples to adequately feed it, has enabled us to gain unprecedented insight into how these deadly tumors progress and ways we can finally stop them.”

Sue, a brain tumor patient from York, died in September 2017 after a seven-year battle with the disease. Her husband, who has been married for 50 years, Geoff, is now an ambassador for the Yorkshire’s Brain Tumor Charity and participates in fundraising events for brain cancer research and awareness.

He welcomes the findings, saying that “Sue fought bravely for seven years without a single word of complaint or self-pity. This is my driver. The types and positions of tumors make this difficult to actually ‘fix’. But it is a scandal that brain tumor survival is no better today than it was 40 years ago.”

“It seems from my experience that a one-size-fits-all approach is currently being taken to treatment and any kind of targeted treatment that is specific to the individual should be an improvement.”

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

The researchers investigate why gliomas evolve into a higher form, and why they survive and continue to grow after treatment.

They collected multiple samples of gliomas over time, as they progressed from low to high, and before and after treatment. Then they watched the cells change and adapt to see if they could find ways to stop them using new drugs.

The team also found that lower grade tumors often develop a new mutation that allows the cells to divide more quickly, potentially catapulting them into a higher form. Image is in the public domain

The mutation and previously unknown cellular interactions can now be addressed with new drugs that stop the tumor cells from progressing and adapting to treatment. In this way, the study has opened up new avenues of research that may yield more effective drugs to offer to patients.

The research was led by Jackson Laboratory (JAX) Florine Deschenes Roux Chair Professor and senior author Dr. Roel Verhaak and Postdoctoral Associate and Jane Coffins Childs fellow first author Dr. Frederick Varn.

dr. Varn says that “by analyzing genetic and transcriptional data from this large cohort of patients, we are beginning to understand how tumors change to adapt to standard treatment.”

“This study has made it clear that not every tumor changes in the same way. Knowing this will allow us to develop therapies in the future that are better tailored to each patient’s disease.”

dr. Verhaak says that “the GLASS project has built tremendous momentum and is only just getting started.”

Also see

This shows brain scans from the study

“We are well on our way to tripling our patient cohort and datasets. We are poised to fully dissect the process of resistance and make significant progress toward better outcomes for patients with glioma.”

About this news about brain cancer research

Author: press office
Source: University of Leeds
Contact: Press Office – University of Leeds
Image: The image is in the public domain

Original research: Closed access.
“Glioma progression is shaped by genetic evolution and interactions in the microenvironment” by Frederick S. Varn et al. Cell


Abstract

Glioma progression is shaped by genetic evolution and interactions in the microenvironment

Highlights

  • Longitudinal glioma evolution follows an IDH mutation-dependent pathway
  • hypermutation and CDKN2A deletions underlie increased proliferation on recurrence
  • Recurrent IDH wild-type neoplastic cells regulate neuronal signaling programs
  • Mesenchymal junctions associate with different myeloid cell interactions

Overview

The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-related cellular and genetic changes, we analyzed RNA and/or DNA sequence data from the transiently separated tumor pairs from 304 adult patients with isocitrate dehydrogenase (IDH) wild-type and IDH mutant glioma.

Tumors recurred in a variety of ways that were dependent on IDH mutation status and attributable to changes in the composition of histological features, somatic changes, and microenvironmental interactions. Hypermutation and Acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells upon recurrence in both glioma subtypes, reflecting active tumor growth.

IDH wild-type tumors were more invasive upon recurrence, and their neoplastic cells showed increased expression of neuronal signaling programs reflecting a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells.

Collectively, these phenotypes associated with recurrence represent potential targets to alter disease progression.

The Valley Voice
The Valley Voicehttp://thevalleyvoice.org
Christopher Brito is a social media producer and trending writer for The Valley Voice, with a focus on sports and stories related to race and culture.

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