summary: In response to treatment, high-grade gliomas remodel the surrounding brain environment, interacting with nearby neurons and immune cells that protect tumor cells and protect them from the body’s natural defenses. .
Source: University of Leeds
The deadliest form of brain cancer comes back as tumors adapt to treatment with help from nearby healthy tissue, say researchers who are trying to find a cure for the disease.
A new study by a global team, including experts from the University of Leeds, has found that in response to treatment, high-grade gliomas remodel the surrounding brain environment, potentially stimulating nearby neurons and Form interactions with immune cells that protect tumor cells. And hide them from the protection of the body.
The team also found that low-grade tumors often develop a new mutation that causes cells to begin dividing more quickly, potentially catapulting them as high-grade ones.
Glioma brain tumors are rare, but the diagnosis is devastating as there is currently no cure. Low-grade gliomas have better survival rates, but often 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.
Associate Professor of Brain Cancer Biology at the University of Leeds School of Medicine and the UK’s lead academic for the study, Dr. Lucy Steed states that “the brain is an extremely complex organ made up of different types of cells, and brain tumors are equally diverse and complex.”
“Learning from patient tissue is the best way to cure a patient’s disease. This study, which required a global effort to obtain enough glioma samples to provide adequate power, gave us unprecedented insights into the How these malignant tumors progress, and the ways in which we may eventually be able to stop them.
Sue, a brain tumor patient from York, died in September 2017 after a seven-year battle with the disease. Her husband of 50 years, Geoff, is now an ambassador for the Brain Tumor Charity of Yorkshire, which participates in events to help raise money for brain cancer research and awareness.
Welcoming the findings, he says that “the case was fought bravely and without complaint or self-pity for 7 years. This is my driver. The type and condition of the tumor make it really difficult to ‘solve’.” But it is a scam that brain tumor survival rates are no better now than they were 40 years ago.”
“From my experience it seems that at this time there is a one-size-fits-all approach to treatment and there should be improvements in any form of treatment targeting the particular individual.”
“The fact that the research is being done has beneficial implications for patients and their families as well. It instills hope.”
Researchers are investigating why gliomas grow as high-grade, and why they survive and continue to grow after treatment.
They collected several samples of gliomas over time as they transitioned from low- to high-grade, and before and after treatment. They then observed how the cells changed and adapted to see if they could find ways to stop them using novel drugs.
Mutations and previously unknown cellular interactions can now be targeted with novel drugs that prevent tumor cells from progressing and adapting to treatment. The study thus opens up new avenues of research that may lead to more effective drugs to offer patients.
The research was led by Jackson Laboratory (JAX) Florin Deschanes Roux Chair Professor and senior author Dr. Roel Verhawk and postdoctoral associate and Jane Coffins Childs fellow first author Dr. Frederick Werne did.
Dr. Werne adds that “by analyzing genetic and transcriptional data from this large cohort of patients, we are beginning to appreciate how tumors are changing to adapt to standard-of-care therapy.”
“This study has made it clear that not every tumor changes in the same way. Knowing this will help us develop therapies that are better tailored to each patient’s disease in the future.”
Dr. Werhawk says that “the Glass Project has created tremendous momentum and is just getting started.”
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“We are well on the way to tripling our patient cohort and dataset. We are ready to broadly dissect the process of resistance and make significant progress toward improved outcomes for patients with glioma.”
About this brain cancer research news
Author: Press Office
Source: University of Leeds
contact: Press Office – University of Leeds
image: Image is in public domain
Basic Research: closed access.
Frederick S. “Glioma progression is shaped by genetic evolution and microenvironment interactions” by Werne et al. room
essence
Glioma progression is shaped by genetic evolution and microenvironment interactions
Highlight
- Longitudinal glioma development follows an IDH mutation-dependent trajectory
- hypermutation and cdkn2a Prevalence increased upon recurrence under deletion
- Recurrent IDH-wild-type neoplastic cells regulate neuronal signaling programs
- Mesenchymal transitions associate with distinct myeloid cell interactions
summary
The factors driving therapy resistance in diffuse glioma are poorly understood. To identify treatment-associated cellular and genetic alterations, we analyzed RNA and/or DNA sequencing data from temporally isolated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant gliomas. did.
Tumors replicated in different ways that were dependent on IDH mutation status and were due to changes in histological feature composition, somatic alterations and microenvironment interactions. Hypermutation and acquired cdkn2a The deletions were associated with increased proliferation of neoplastic cells upon recurrence in both glioma subtypes, reflecting active tumor growth.
IDH-wild-type tumors were more aggressive upon recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs indicating a potential 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 recurrence-associated phenotypes represent potential targets to alter disease progression.
(This story has not been edited by seemayo staff and is published from a rss feed)