Though the detailed mechanisms are unknow about how DNA‐PKcs and PARP make the ecDNA and whether the chromothripsis‐induced ecDNA is the common mechanism for all the chemotherapeutic drugs, noting that chromothriptically initiated rearrangements are often resulted from chemotherapeutic drugs, the combinational targeted therapy with both DNA‐PKcs and PARP inhibitors may represent an effective regimen to prevent cancer progression or chemo‐resistance. The gene discussed is PARP1; the disease is cancer.