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Cells from rapidly growing, highly metastatic tumors often contain numerous rings of extrachromosomal DNA (ecDNA). This circular DNA frequently carries oncogenes—genes that promote cancer. Researchers have long sought vulnerabilities in these DNA rings in an effort to stop their harmful activity.

An international team led by Dr. Anton Henssen, group leader of the Genomic Instability in Pediatric Tumors lab at the Experimental and Clinical Research Center, a joint institution of Charité—Universitätsmedizin Berlin and the Max Delbrück Center, has now identified a potential target.

As the researchers report in Nature Genetics, the DNA rings lose their activity when they become trapped outside the cell nucleus in micronuclei—a process that also occurs naturally in cancer cells. Consequently, active compounds that drive ecDNA into micronuclei may help treat some metastatic cancers.

In addition to Henssen, the study's senior authors are Dr. Howard Chang and Dr. Paul Mischel of Stanford University in California. Since December 2024, Chang has served as chief scientific officer at Amgen. Mischel leads the eDyNAmiC team within the international Cancer Grand Challenges initiative, which seeks to better understand the key role of circular DNA in cancer. The current study was conducted as part of that project.

When a cell divides, its chromosomes are normally distributed evenly between two daughter cells. ecDNA behaves differently. "These DNA rings lack the structures needed for orderly transport," Henssen explains.

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