Scientists Find Achilles' Heel in Cancer's Rogue Extrachromosomal DNA

Researchers at Memorial Sloan Kettering identified that extrachromosomal DNA (ecDNA), found in roughly 1 in 6 human cancers, is especially fragile at TA repeat regions. Blocking the repair protein Polθ with an experimental inhibitor caused ecDNA to accumulate damage and be lost from cancer cells, while cells without ecDNA were largely unaffected.

• ecDNA occurs in roughly 1 in 6 human cancers and drives faster tumor growth
• TA repeats fold into fragile cross-shaped structures that break easily
• FANCM and Polθ protect ecDNA before and after breaks
• Polθ inhibitors are already in clinical development