Five advancements in brain tumor research over the past year

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CAR-T glioblastoma

In 2023, it is estimated that 24,810 adults in the U.S. will be diagnosed with a primary malignant tumor 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 lot of research being conducted around brain tumors that could lead to the development of new treatments, and in this article, we have listed five recent advancements in brain tumor research.

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

Additionally, certain primary brain tumors can rapidly spread to other areas of the body, resulting in these treatments becoming 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 promising advancements in brain tumor research over the past year.

Table of contents

    Discovery of brain tumor subtypes could help identify new therapies 

    The majority of 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 RCSI University of Medicine and Health Sciences has discovered three new subtypes of brain tumor that could help to identify new and effective therapies, and further investigation of these subtypes could result in different patients receiving precision medicine treatment that is specific to the cells in their own individual tumor. 

    The research, published in Annals of Oncology, has identified that glioblastoma tumors can be placed into three separate categories based on the different kinds of non-cancer cells, such as immune cells and blood vessel cells, that can be found within the tumor. 

    Senior author and lead 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 vital that new treatments be developed. Targeted treatment or ‘precision medicine’ has the potential to improve outcomes for these patients. We hope further analysis of the tumor subtypes identified in this research will provide the data needed to support future glioblastoma clinical trials in Ireland.”

    This research has also led to a new project, which Byrne is coordinating, called GLIORESOLVE, whereby ten individual research projects will focus on identifying new drugs that might work in the different subtypes of glioblastoma, identifying new tumor microenvironment-focused drug targets, and making tumors more sensitive to immune therapies. The consortium will establish a new precision medicine platform that can potentially lead to novel treatment options for glioblastoma.

    3D genome mapping could help treat pediatric brain tumors

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

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

    “In this study, we used these new technologies to reveal structural components of the ependymoma genome that can be linked to genes essential for the survival of ependymoma tumor cells. This gives us a broad range of new treatment targets that have not been previously associated with this tumor type. Our results encourage future studies that further evaluate these targets, which will then help us discover and test new drugs that can treat ependymoma more effectively and without the unwanted effects of current treatments,” said Chavez. 

    The current standard-of-care treatment for ependymomas is surgery followed by radiation therapy, which poses the risk of long-term neurological side effects and secondary cancers, signaling an unmet need for new treatment options. 

    As well as potentially laying the foundation for further studies that could lead to new therapies for ependymoma, the researchers are also planning to look at other pediatric cancers, as there are many that lack therapeutic options. 

    New research has uncovered a key culprit behind pediatric brain cancer metastasis

    In more brain tumor research specifically looking at pediatric tumors, physician-scientists from the University of Pittsburgh School of Medicine Department of Neurological Surgery and UPMC Children’s Hospital of Pittsburgh have discovered that medulloblastomas – the most common malignant pediatric brain tumors – hijack a skill that normal brain cells use during their early development and then manipulate it to help tumors spread.

    Medulloblastomas most commonly form in the cerebellum – the bottom part of the brain located at the back of the skull – and are usually treated with surgery followed by radiation and chemotherapy. However, some types of medulloblastomas often metastasize, or spread, to tissues and organs beyond where the tumor originated, meaning these treatments no longer work. 

    In order to learn how medulloblastoma cells metastasize, researchers leveraged medulloblastoma patient data and experimental mouse data to identify a gene, SMARCD3, whose levels were significantly higher in metastatic tumors compared to tumors that had not spread. They also showed that SMARCD3 hijacks neurodevelopmental signaling – used by healthy brain cells during early cerebellar development before being shut off once the cerebellum matures – to promote tumor cell spreading. 

    “We’ve been thinking of medulloblastoma metastasis from the perspective of neuroscience and

    understanding how abnormal brain development causes and influences brain tumors. This cancer neuroscience approach helped us to pinpoint the fundamental mechanisms, which allow us to develop safe, effective, and personalized medical treatments for children with this devastating brain cancer,” said Baoli Hu, assistant professor of neurological surgery at the University of Pittsburgh. 

    Based on these new findings, researchers also tested a drug called dasatinib, which has been approved to treat leukemia in the clinic. In a mouse model of medulloblastoma, it was found that dasatinib killed metastatic tumors but did not greatly harm normal brain cells, meaning it could be safe for treating patients with medulloblastoma metastasis. 

    New research could pave the way for a new type of drug-containing nanoparticle to treat brain tumors

    Scientists from the University of Nottingham in the U.K. and Duke University in the U.S. have discovered that many of the blood vessels that feed high-grade glioma brain tumors contain high levels of low-density lipoprotein (LDL) receptors (LDLR) on them. 

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

    But these finding could allow for a new type of drug-containing nanoparticle to be used in the treatment of gliomas to starve the tumors of the energy they use to grow and spread, as well as to cause other disruptions to their adapted existence, which could even result in the tumors killing themselves. 

    In the study, researchers examined tissue microarrays from intra- and inter-tumor regions of 36 adult 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 to test LDLR-targeted nanoparticle uptake, retention and cytotoxicity. 

    The researchers were able to show widespread LDLR expression in both adult and pediatric cohorts and categorize the intra-tumor variation observed between the core and either rim or invasive regions of adult high-grade gliomas. 

    A novel gel that was shown to stop brain tumors in mice could also offer hope for humans

    It was recently announced that a novel gel medication managed to cure 100% of mice that had an aggressive brain cancer, which could potentially lead to a new treatment strategy for patients diagnosed with glioblastoma, as the hydrogel could supplement current treatments. 

    The researchers combined an anticancer drug and an antibody in a solution that self-assembles into a gel, intended to fill the tiny grooves left after a brain tumor is surgically removed. The benefit of the gel is that it can reach areas that surgery might miss and that current drugs struggle to reach, which will kill any lingering cancer cells and suppress tumor growth. 

    Additionally, it was found that the gel triggered an immune response in mice that their body struggles to activate on its own when fighting glioblastoma, and when researchers rechallenged surviving mice with a new glioblastoma tumor, their immune system alone beat the cancer without the need for additional medication. This suggests that, not only does the gel fight cancer, it also helps to rewire the immune system to discourage recurrence using immunological memory.

    The gel solution consists of nano-sized filaments made with paclitaxel – a U.S. Food and Drug Administration (FDA)-approved drug for breast, lung and other cancers. These filaments provide a vehicle to deliver an antibody called aCD47. By evenly blanketing the tumor cavity, the gel releases medication steadily over several weeks, with its active ingredients remaining close to the injection site. 

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

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