Biotechnology

Five recent advances in brain tumor research

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By 2023, an estimated 24,810 adults in the US will be diagnosed with primary malignant tumors of the brain and spinal cord. There is currently no cure for brain tumors and current treatment options are mostly limited to surgery, radiation therapy and chemotherapy. However, there is a great deal of research being done around brain tumors that could lead to the development of new treatments, and in this article, we have listed five of the most recent advances in brain tumor research.

Successfully treating brain tumors using current standard-of-care treatment options, which – as previously mentioned – include surgery, radiation therapy and chemotherapy, can be challenging. This is caused by several factors, such as the body’s blood-brain barrier preventing some types of chemotherapy, and surgery not being an option due to tumor placement; for example, if it is near a vital structure or an inaccessible part of the brain.

In addition, certain primary brain tumors can quickly spread to other areas of the body, rendering these treatments ineffective.

This means there is an unmet need for new approaches to treating brain tumors, and here we take a look at some of the most promising advances in brain tumor research over the past year.

The discovery of brain tumor subtypes could help identify new therapies

Most patients with glioblastoma – the deadliest and most common type of primary malignant brain tumor in adults – are currently treated in the same way, with treatment options mostly limited to surgery, radiation and chemotherapy.

But recent brain tumor research led by the RCSI University of Medicine and Health Sciences has found three new subtypes of brain tumors that could help identify new and effective therapies, and further investigation of these subtypes could result in different patients receiving precision drug treatment. specific. to the cells in their own individual tumors.

Study, published in the Annals of Oncologyhave identified that glioblastoma tumors can be placed into three separate categories based on the different types of non-cancerous cells, such as immune cells and vascular cells, that can be found within the tumor.

Senior author and principal investigator, Annette Byrne, head of the RCSI Precision Cancer Medicine Group, said: “Glioblastoma patients currently have a poor prognosis due to limited treatment options so it is important to develop new treatments. Targeted treatment or ‘precision medicine’ has the potential to improve outcomes for these patients. We hope that further analysis of the tumor subtypes identified in this study will provide the necessary data to support future glioblastoma clinical trials in Ireland.”

This research has also led to a new project, coordinated by Byrne, called GLIORESOLVE, in which ten individual research projects will focus on identifying new drugs that may act on different glioblastoma subtypes, identifying drug targets focused on novel tumor microenvironments, and make tumors more sensitive to immune therapy. The consortium will establish a new precision medicine platform that has the potential to lead to new treatment options for glioblastoma.

3D genome mapping could help treat childhood brain tumors

In April 2023, it was announced that researchers are now leveraging the latest technology to uniquely look at ependymoma, which is one of the deadliest childhood brain tumors and difficult to cure with currently available treatments.

The ‘latest technology’ here involves using a new technique called 3D genome mapping, which allows researchers to visualize how genes are arranged and regulated in tumor cells. According to Lukas Chavez, an assistant professor at Sanford Burnham Prebys who led the research, the technology allowed them to visualize the three-dimensional structure of the genome rather than simply analyzing the linear sequence of DNA, as was previously the standard approach to genomics.

“In this study, we used this new technology to uncover structural components of the ependymoma genome that can be associated with genes critical for ependymoma tumor cell survival. This provides us with a variety of new treatment targets that have not previously been associated with this type of tumor. Our results encourage future research that further evaluates this target, which will then help us discover and test new drugs that can treat ependymoma more effectively and without the unwanted effects of current treatments,” Chavez said.

The current standard of care for ependymoma is surgery followed by radiation therapy, which carries risks of long-term neurological side effects and secondary cancer, indicating an unmet need for new treatment options.

As well as potentially laying the groundwork for further studies that could lead to new therapies for ependymomas, the researchers also plan to look into other childhood cancers, as there are many therapeutic options lacking.

In more brain tumor studies looking specifically at childhood tumors, physician-scientists from the University of Pittsburgh School of Medicine Department of Neurosurgery and Children’s Hospital UPMC Pittsburgh have found that medulloblastomas – the most common malignant childhood brain tumor – hijack normal skills. brain cells use during their early development and then manipulate them to help tumors spread.

Medulloblastoma most often forms in the cerebellum – the lower part of the brain that lies at the back of the skull – and is usually treated with surgery followed by radiation and chemotherapy. However, some types of medulloblastoma often metastasize, or spread, to tissues and organs outside the tumor’s origin, which means these treatments no longer work.

To study how medulloblastoma cells metastasize, the researchers used medulloblastoma patient data and mice data to identify a gene, SMARCD3, whose levels were significantly higher in metastatic tumors than in tumors that had not spread. They also showed that SMARCD3 hijacks neurodevelopmental signaling – used by healthy brain cells during early cerebellar development before being turned off after the cerebellum matures – to promote tumor cell spread.

“We have considered medulloblastoma metastases from a neuroscientific perspective and

understand how abnormal brain development causes and affects brain tumors. This cancer neuroscience approach helped us define the underlying mechanisms that will allow us to develop safe, effective and personalized medical treatments for children with this devastating brain cancer,” said Baoli Hu, assistant professor of neurosurgery at the University of Pittsburgh.

Based on these new findings, the researchers also tested a drug called dasatinib, which has been approved to treat leukemia at the clinic. In a mouse model of medulloblastoma, it was found that dasatinib killed metastatic tumors but was less damaging to normal brain cells, meaning it could be safe to treat patients with metastatic medulloblastoma.

The new research could pave the way for new types of nanoparticles containing drugs to treat brain tumors

Scientists from the University of Nottingham in the UK and Duke University in the US have found that many of the blood vessels that feed high-grade glioma brain tumors contain high levels of low-density lipoprotein (LDL) receptors (LDLR).

Nearly half of gliomas are classed as high-grade gliomas and, because of their aggressive nature, the median survival outcome is 4.6 months without treatment and about 14 months with treatment, which currently includes surgery, radiation, and chemotherapy.

But these findings allow new types of drug-containing nanoparticles to be used in the treatment of gliomas to starve tumors of the energy they use to grow and spread, as well as cause other disruptions to their adapted existence, which can even result in tumors killing themselves.

In the study, the investigators examined tissue microarrays of the intra- and intertumor regions of 36 adult patients and 133 pediatric patients to confirm LDLR as a therapeutic target, and expression levels in three representative cell line models were also tested to confirm their future utility for testing. Absorption, retention, and cytotoxicity of LDLR target nanoparticles.

Investigators were able to demonstrate widespread LDLR expression in adult and pediatric cohorts and categorize the observed intra-tumor variation between core and peripheral or invasive areas of adult high-grade gliomas.

A new gel shown to stop brain tumors in mice could also give hope to humans

It was recently announced that a new gel drug successfully cures 100% of mice suffering from aggressive brain cancer, which could potentially lead to new treatment strategies for patients diagnosed with glioblastoma, as hydrogels can complement current treatments.

The researchers combined anticancer drugs and antibodies in a solution that self-assembled into a gel, intended to fill in the tiny grooves left after brain tumors are surgically removed. The benefit of this gel is that it can reach areas that surgery and drugs might miss that are currently difficult to reach, which will kill any remaining cancer cells and suppress tumor growth.

In addition, it was found that the gel triggered an immune response in mice whose bodies struggled to activate on their own while battling glioblastoma, and when the researchers challenged the surviving mice with new glioblastoma tumors, their own immune systems defeated the cancer without the need for additional drugs. This shows that, the gel not only fights cancer, but also helps repair the immune system to prevent recurrence using immunological memory.

The gel solution consists of nano-sized filaments made with paclitaxel – a drug approved by the US Food and Drug Administration (FDA) for breast, lung, and other cancers. This filament provides the vehicle for delivering an antibody called aCD47. By uniformly covering the tumor cavity, the gel releases drug stably over several weeks, with the active ingredient remaining near the injection site.

The gel is designed to work in tandem with surgery, as applying it directly to the brain without surgical removal of the tumor only results in a 50% survival rate.

New technologies related to brain tumors (supported by IN-PART)

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