Researchers Identify Key Genes Influencing Brain Tumor Spread, Opening Doors for New Therapies

A groundbreaking international study led by Uppsala University has elucidated critical mechanisms behind the invasive behavior of glioblastoma, the most common and aggressive primary brain cancer in adults. Unlike many cancers that metastasize to distant sites, glioblastoma predominantly spreads locally within the brain tissue, making it difficult to treat. Understanding how these tumors infiltrate brain tissue is vital for developing more effective therapies.

The research, recently published in Nature Communications, reveals that glioblastoma cells adopt distinct states that influence their invasion routes. Some tumor cells tend to grow along blood vessels, a process associated with specific gene activity, while others diffusely infiltrate the surrounding brain tissue. The team employed advanced techniques like single-cell profiling and spatial protein detection on both mouse models and patient tumor samples. Their analysis uncovered a strong correlation between cell states and invasion patterns.

Key genes were identified as regulators of these invasion behaviors. The gene ANXA1 was linked to tumor cells invading blood vessels, whereas HOPX and RFX4 were associated with the widespread infiltration of brain tissue. Functional experiments knocking out these genes caused a shift in invasion patterns and even prolonged survival in preclinical models, highlighting their potential as therapeutic targets.

Further, the presence of proteins derived from these genes was detected in patient tissue samples, with higher levels of ANXA1 and RFX4 correlating with poorer prognoses. These findings suggest that they could serve as valuable biomarkers for predicting patient outcomes.

The study underscores the heterogeneity of glioblastoma, emphasizing that different cell types within the tumor contribute to its invasive capacity. As Professor Sven Nelander from the Department of Immunology, Genetics and Pathology explains, understanding these diverse invasion strategies offers promising avenues for targeted treatments that could improve survival rates.

Collaborating institutions included Queen Mary University of London and Dana-Farber Cancer Institute in Boston, reflecting the global effort to tackle this devastating disease.

This research advances our knowledge of glioblastoma’s invasive nature and opens new pathways for the development of precision therapies aimed at mitigating tumor spread in the brain.