Glioblastoma is indeed one of the most aggressive and lethal forms of brain cancer, characterized by its rapid growth and resistance to conventional therapies. The presence of extrachromosomal DNA (ecDNA) in glioblastoma and other types of cancer is a relatively recent discovery that has significant implications for our understanding of cancer biology and treatment strategies. EcDNA are circular units of DNA that exist outside the chromosomes within a cell. Unlike chromosomal DNA, ecDNA can replicate independently and often contains genes that can drive cancer progression, including oncogenes and drug-resistance genes. The presence of ecDNA can lead to high levels of genetic diversity within tumors, contributing to cancer evolution and the development of resistance to therapies. Here’s a breakdown of the points: 1. **Driver of Cancer Evolution**: EcDNA can carry multiple copies of oncogenes, which are genes that, when mutated or overexpressed, can promote the uncontrolled growth of cancer cells. Because ecDNA can replicate independently of chromosomal DNA, it can rapidly amplify these oncogenes, leading to accelerated tumor evolution and heterogeneity. This makes it difficult to treat glioblastoma, as different parts of the tumor may respond differently to therapies. 2. **Mediator of Therapy Resistance**: The genes on ecDNA can include those that confer resistance to chemotherapy and targeted therapies. As these genes are amplified, the cancer cells become more adept at surviving in the presence of drugs designed to kill them. This is a major challenge in treating glioblastoma, where recurrence after initial treatment is common. 3. **Prognostic Marker**: The presence and characteristics of ecDNA in cancer cells can provide information about the aggressiveness of the disease and potential treatment outcomes. By analyzing ecDNA, clinicians can better predict which patients have more aggressive tumors and tailor treatments accordingly. 4. **Emerging Clinical Trials**: Given the role of ecDNA in driving glioblastoma progression and therapy resistance, researchers are exploring ways to target ecDNA in clinical trials. This could involve strategies to disrupt the replication of ecDNA, degrade ecDNA, or target the oncogenes carried on ecDNA. By focusing on ecDNA, these trials aim to find new ways to combat glioblastoma and improve patient outcomes. While studying ecDNA in cancer is a promising field, it is also complex and requires further research to translate findings into effective treatments. The unique challenges posed by glioblastoma, such as its location in the brain and its highly invasive nature, make the development of such targeted therapies particularly urgent. As our understanding of ecDNA in cancer grows, it holds the potential to revolutionize the way we approach the diagnosis and treatment of glioblastoma and other aggressive cancers.  Image by freepik,  read the full article at https://www.annalsofoncology.org/article/S0923-7534(24)00085-1/fulltext