Attack extrachromosomal DNA, the engine of oncogene amplification
Many aggressive tumours keep their cancer genes on free-floating DNA circles that let them dial resistance up and down at will. Drugs that break the circles or the cell's tolerance of them are a new frontier.
ecDNA carries EGFR, MYC, MDM2, and CDK4 amplicons in glioblastoma, sarcoma, and gastric cancer, associates with poor survival, and enables rapid drug resistance by copy-number fluctuation. The eDyNAmiC Cancer Grand Challenge team reported CHK1 dependence and transcription–replication conflicts in ecDNA+ cells (2024).
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