A breakthrough in understanding how and why some cancerous tumors are particularly aggressive and unresponsive to treatments has put the blame on mischievous strands of DNA.
The discovery implicates several documented forms of cancer, including breast, lung and brain, and also offers hope for identifying and treating these tumors in future patients.
The center of the discovery is what is called extrachromosomal (external to the chromosome) DNA, or ecDNA for short. Our genetic coding sequences are tightly wrapped around histones using 23 pairs of chromosomes. This keeps the code small enough to fit within the nucleus of a cell.
In some cases, DNA can break chromosomes and separate inside the nucleus, a rare phenomenon that was once thought to be insignificant in the development of cancer. However, in a series of three papers published by a coalition of US-British researchers, these cDNA fragments were found to be present in tumor cells of some of the most aggressive and treatment-resistant cancers.
“This is not just a discovery about what can make cancer so serious, it actually opens the door to a new set of therapies,” said Paul Mischel, professor of pathology at Stanford University, author of one of the three articles, and director of the laboratory in which all three were carried out.
“There is a path forward to develop new treatments because this type of DNA is different and creates different vulnerabilities,” he said. told the Guardian.
EcDNA fragments, find In 17.1% of all tumors examined in studies, they carried cancer-causing genes and other genes that suppress the immune system. Studies have also found that ecDNA can replicate chaotically, which also leads to cancer growth.
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The tumor cells were sometimes find to contain many more ecDNA fragments than others, meaning that once separated from the DNA-histone-chromosome structure, they do not divide evenly with the cell. Some daughter cells inherit much more ecDNA than others.
The good news is that drugs called CHK1 inhibitors have been find to selectively destroy ecDNA-containing tumor cells in mice when administered in combination with a traditional anticancer drug.
David Scott, director of Cancer Grand Challenges at Cancer Research UK, which funded the studies, noted that this treatment, if seen in humans, would have the effect of “cutting the lifeline” on which support these tumors to escape traditional and newer immunotherapy. treatments.
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“Survival of many of the most aggressive cancers depends on ecDNA, and as these cancers progress, ecDNA drives their resistance to treatment, leaving patients with few options. By targeting ecDNA, we could cut the lifeline from these relentless tumors, turning a terrible prognosis into a treatable one.
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