Rogue DNA Rings Offer New Hope in Fight Against Aggressive Brain Cancer
A groundbreaking study reveals that “rogue” rings of DNA, known as extrachromosomal DNA (ecDNA), play a critical role in driving the growth of glioblastoma, the most common and aggressive form of adult brain cancer, potentially opening avenues for earlier diagnosis and more effective treatment.
Glioblastoma remains one of the most challenging cancers to treat, with a median survival rate of just 14 months and limited progress in improving outcomes over recent decades. This new research, published today in Cancer Revelation, suggests that ecDNA is not merely a byproduct of cancer advancement, but a key driver of tumor aggressiveness and treatment resistance.
This international study,led by researchers at Queen Mary University of London and Stanford University,and part of the Cancer Grand Challenges’ team eDyNAmiC,sheds new light on this complex process. The $25 million eDyNAmiC consortium brings together experts in cancer, clinical research, evolutionary biology, computer science, and mathematics to decipher ecDNAS role and identify potential therapeutic targets.
Researchers approached the study like “archaeologists,” as described by Dr. Benjamin Werner, senior author and group leader at the Barts Cancer Institute. “Rather than taking a single sample, we excavated multiple sites around the tumor, allowing us to build computational models describing how they evolved. We simulated millions of diffrent scenarios to reconstruct how the earliest ecDNAs emerged, spread, and drove tumor aggressiveness, giving us a clearer picture of the tumor’s origins and progression.”
EGFR: A Key driver of Tumor Growth
the analysis revealed that the majority of ecDNA rings contained EGFR, a gene known to promote cancer growth. Critically, EGFR ecDNA appeared early in the cancer’s evolution, even preceding tumor formation in some patients.Furthermore, the researchers found that EGFR frequently acquired additional mutations, such as the EGFRvIII variant, which further accelerated tumor growth and increased resistance to therapies.
“These subtle mechanisms show that there may be a window of prospect to detect and treat the disease between the first appearance of EGFR ecDNA and the emergence of these more aggressive variants,” explained Dr.Magnus Haughey, a postdoctoral researcher involved in the study.”If scientists can develop a reliable test to detect early EGFR ecDNA – for example through a blood test – it could enable them to intervene before the disease becomes harder to treat.”
The study also confirmed that ecDNA can carry multiple cancer-driving genes together, each influencing how tumors evolve and respond to treatment. This finding underscores the potential for personalized treatment strategies based on a tumor’s unique ecDNA profile..
A New Era in Glioblastoma Treatment?
Experts believe this research represents a significant step forward in understanding glioblastoma. According to Professor Charlie Swanton, Deputy Clinical Director at The Francis Crick Institute, the findings suggest that ecDNA is “not just a passenger in glioblastoma, but an early and powerful driver of the disease.” He added that tracing the origins and evolution of ecDNA could lead to earlier detection and intervention, potentially transforming how this devastating cancer is diagnosed and treated.
Professor Paul Mischel, MD, of Stanford Medicine, echoed this sentiment, noting that the study reveals a new insight into ecDNA’s role in tumor development. “The findings here show that in glioblastoma, there is an early event driven by ecDNA that could potentially be more actionable, raising the possibility that glioblastoma is another cancer for which earlier detection and intervention based upon ecDNA may be possible.”
Dr.David Scott,Director of Cancer Grand Challenges,emphasized the importance of this type of bold,interdisciplinary research. “By unravelling the evolutionary history of ecDNA in glioblastoma, team eDyNAmiC is not only deepening our understanding of one of the most devastating cancers but also illuminating new paths for earlier detection and treatment.” The team will continue to investigate the role of ecDNA across a range of cancer types, seeking to unlock further opportunities for improved diagnosis and smarter treatments.
