Innovative Map of Tumor Cells Enhances Personalized Brain Cancer Therapies

Scientists from City of Hope National Medical Center have made a significant breakthrough in brain cancer research by developing a comprehensive map of tumor cells. This pioneering study demonstrates that analyzing genetic material near chromosomes, specifically extrachromosomal DNA (ecDNA), can predict how cancer-driving genes reconfigure DNA and influence the tumor microenvironment. The research highlights that a high prevalence of ecDNA, along with cancer-related proteins like EGFR and p53, can lead to a hypoxic tumor microenvironment—characterized by reduced oxygen levels—that is associated with cancer progression, resistance to treatments, and poorer clinical outcomes.

The study employs advanced techniques such as spatial transcriptomics, which maps DNA activity in the tumor's spatial context, combined with genomic data. This approach enables researchers to identify groups of cells within the tumor that share an ancestry but have acquired additional mutations, providing insights into tumor evolution.

Focusing on gliomas—tumors occurring in the brain or spinal cord—the team conducted bulk RNA sequencing, DNA sequencing of tumor and normal tissue, and spatial transcriptomics on small tumor samples. Their comprehensive analysis revealed both common and unique characteristics of the tumor microenvironment, establishing an integrated framework that can be utilized in future research.

The findings suggest that ecDNA drives rapid proliferation of cancer cells outside of the chromosomes, contributing to genetic instability and varied tumor cell populations within a single tumor. This dynamic nature of ecDNA allows cancer cells to adapt and reprogram their genomes in response to environmental changes and therapies, making them more resilient.

Dr. David Craig emphasizes that understanding these mechanisms offers promising pathways for developing more precise, individualized treatments. Co-author Dr. Gabriel Zada notes that while the current study focuses on brain cancers, the underlying principles and techniques could eventually enable clinicians to craft tailored therapies for various cancer types.

This research underscores the importance of exploring ecDNA's role in tumor biology and how it affects tumor evolution and therapy resistance. The study has been published in Nature Communications and marks a step forward in the quest for personalized cancer treatments.

For more details, visit the original publication: Nature Communications.