ALEMs are most frequently seen in GBM and low-grade gliomas and occur not only in EGFR but also in PDGFRα and ERBB2, which highlights the diversity of mechanisms by which eccDNA is involved in drug resistance to targeted therapies in GBM.259 In addition to chemotherapy, eccDNA has also been associated with radiotherapy resistance in GBM. This evidence concerns the gene ERBB2 and glioblastoma.