Unlocking the Brain: New Research Is Changing How Tumors Are Diagnosed and Treated

Each year, about 90,000 people in the U.S. are diagnosed with a brain tumor, including roughly 25,000 with cancerous tumors. These tumors are especially challenging because in the brain, even small changes can affect critical functions like movement, speech and memory.

Across Mayo Clinic's campuses in Rochester, Arizona and Florida, researchers are advancing the understanding of brain tumor biology, improving diagnostic precision and developing new treatment approaches to support timely, personalized care.

Reading a brain tumor's molecular "fingerprint"

DNA methylation profiling is helping redefine how brain tumors are diagnosed and classified. By analyzing chemical markers on DNA, this approach creates a "molecular fingerprint" that can reveal a tumor's type, behavior and potential treatment options. This provides insight beyond what can be seen under a microscope.

In a large international study, Mayo Clinic researchers expanded the Heidelberg DNA methylation classifier. The classifier compares a patient's tumor profile to a reference database of central nervous system CNS tumors. The updated tool identifies 184 tumor subclasses (up from 91), achieves 95% accuracy and detects chromosome changes in a single test. For patients, this means one sample may help answer multiple diagnostic questions.

Methylation profiling complements traditional pathology by adding an objective layer of information, especially when findings are unclear. This integrated approach combines molecular, microscopic and clinical data to improve diagnostic accuracy.

It also may help guide care after surgery. In a study of nearly 2,000 meningiomas, Mayo Clinic investigators used methylation-based models to estimate the chance a tumor would recur and potential benefit from radiation, helping group tumors into those that may:

• Benefit from additional radiation.
• Be monitored closely.
• Require alternative treatments, such as clinical trials.

Together, these advances support a more precise approach to brain tumor care.

Understanding pediatric and AYA brain tumors to personalize treatments

Each year, about 12,000 adolescents and young adults (AYAs), which are people between the ages 15 and 39, are diagnosed with brain and other CNS tumors. Tumors in this group often behave differently from those in older adults, yet they remain understudied.

In one Mayo Clinic study, researchers analyzed thousands of tumor samples to better understand these differences. They found that AYAs can develop a mix of tumor types, some more common in children and others typically seen in older adults, as well as tumors more specific to this age group. These tumors also showed distinct biological patterns, which may help improve classification, diagnosis and more personalized treatment.

A second Mayo-led study focused on meningiomas, one of the most common brain tumors in this age group. Researchers found that tumors in pediatric and AYA patients tend to be less aggressive than those in older adults. However, commonly used prediction tools — largely developed using adult data — were less accurate for younger patients. When adjusted using age-specific data, these tools performed significantly better.

These findings highlight the importance of including AYA and younger patients in research to improve diagnostics and guide care.

Turning the brain's barrier into a gateway

For aggressive brain tumors such as glioblastoma, delivering treatments across the protective blood–brain barrier (BBB) remains a major challenge. In a recent review, Mayo Clinic investigators highlight emerging strategies to temporarily and precisely open the BBB, allowing therapies to better reach tumor cells. Early studies suggest these approaches can increase drug delivery to brain tissue by two- to nearly six-fold.

In a separate study, Mayo Clinic researchers examined how well two different drugs reached tumor tissue during surgery. They found that drug delivery varied widely, not only between drugs but also within different areas of the same tumor. Imaging did not always predict how much of a drug reached the tumor, underscoring the complexity of treatment delivery.

Mayo Clinic researchers also developed an experimental nanotherapy that uses microscopic particles to deliver two cancer drugs directly to brain tumors. In preclinical models of glioblastoma, this approach extended survival.

Combining radiation and drug therapies

Diffuse intrinsic pontine glioma (DIPG) is a serious childhood brain tumor. Radiation therapy remains the standard treatment, but it is not curative. Researchers are exploring targeted therapies that deliver treatment directly to tumor cells using specific markers. In preclinical models, combining radiation with these approaches improved tumor cell damage and slowed growth. Further research is needed to confirm safety and effectiveness in patients.

Researchers also are working to better match patients with appropriate radiation treatments. In a study of stereotactic radiosurgery, a highly focused form of radiation, Mayo Clinic investigators identified factors linked to short-term survival, including overall health, control of cancer outside the brain and neurological symptoms. These insights may help guide more personalized treatment decisions.

In another study of clival chordoma, a rare skull base cancer, researchers found that follow-up scans after proton beam therapy can sometimes appear to show tumor growth when changes are actually temporary treatment effects. This phenomenon, known as pseudoprogression, may reflect inflammation or healing, and it can later stabilize or resolve. Recognizing these patterns may help avoid unnecessary procedures while ensuring appropriate monitoring.

Advancing immunotherapy and targeted treatments

Understanding how the immune system interacts with brain tumors is an important area of research. In a recent study, Mayo Clinic researchers identified a protein called galectin-9 that may help immune cells recognize and interact with tumor cells in gliomas. The findings provide new insight into tumor biology and may help guide future immunotherapy approaches.

These advances reflect Mayo Clinic's commitment to advancing brain tumor research and care. By connecting discoveries in the laboratory with patient care, researchers are working to improve diagnosis, guide treatment decisions and move closer to more effective therapies.