Topoisomerase II inhibitors

These drugs stabilize the DNA-Topo II complex, preventing DNA re-ligation → DNA double-strand breaks → cancer cell death.

Classes & Examples

• Anthracyclines (intercalate DNA + inhibit Topo II):

  • Doxorubicin, Daunorubicin, Idarubicin (used in AML, lymphomas, sarcomas).
  • Side Effects: Cardiotoxicity (dose-dependent), myelosuppression.

• Epipodophyllotoxins (non-intercalating):

  • Etoposide (VP-16), Teniposide (used in AML, ALL, lung cancer).
  • Side Effects: Secondary leukemias (t-AML with *MLL/KMT2A* rearrangements).

• Others:

  • Mitoxantrone (less cardiotoxic anthracycline analog).

Clinical use:

They are used to treat various cancers, including: Acute myeloid leukemia (AML), Lung cancer, Lymphomas, Testicular cancer

Key point:

Topoisomerase II inhibitors induce apoptosis in cancer cells by preventing proper DNA repair, making them effective anticancer agents. However, they can also cause secondary leukemias due to DNA damage in healthy cells