Our findings revealed higher expressions of both total and S1106 phosphorylated TOP2A proteins in the primary tumors than in the normal control tissues, suggesting the importance of S1106 phosphorylated TOP2A protein in tumorigenesis and drug resistance, and the necessity of exploring S1106 phosphorylated TOP2A protein-related mechanisms to design new therapeutic strategies for cancers resistant to TOP2A targeted drugs. Here, TOP2A is linked to cancer.