TOP2A (DNA topoisomerase II alpha) is a critical enzyme that resolves DNA topological stress by creating transient double-stranded breaks, passing intact DNA strands through the break, and religating the DNA 1. This decatenating activity is essential for DNA replication and transcription, particularly under high-output conditions 1. TOP2A functions as part of MYC-assembled 'topoisome' complexes that enhance topoisomerase activity at promoters and enhancers 1. Dysregulated TOP2A expression is associated with multiple malignancies including hepatocellular carcinoma, breast, prostate, colon, and lung cancers 2. TOP2A gene amplification occurs frequently adjacent to HER-2 in breast tumors and correlates with both chemotherapy sensitivity and resistance depending on copy number status 3. Elevated TOP2A expression promotes tumor progression and chemotherapy resistance; for example, in nasopharyngeal carcinoma, the USP7/KDM5B/ZBTB16/TOP2A axis regulates cisplatin resistance 4. In hepatocellular carcinoma, EZH2-mediated epigenetic silencing of miR-139-5p increases TOP2A expression, inhibiting cellular senescence 5. Clinically, TOP2A amplification predicts anthracycline chemotherapy response, yet overexpression indicates poor prognosis and disease recurrence risk 2. TOP2A deficiency impairs trophoblast function and embryonic development, linking it to recurrent spontaneous abortion 6. These findings establish TOP2A as a key prognostic biomarker and therapeutic target across multiple cancer types.