What is the mechanism of action (MOA) of anthracyclines?

Anthracyclines exert their therapeutic effects primarily through the inhibition of topoisomerase II, an essential enzyme that plays a significant role in DNA replication and repair. By interrupting the action of this enzyme, anthracyclines prevent the unwinding of DNA necessary for replication, which leads to the formation of DNA double-strand breaks. This disruption ultimately results in cell cycle arrest and apoptosis, particularly in rapidly dividing cancer cells.

Additionally, anthracyclines intercalate between DNA base pairs, causing further structural alterations to the DNA helix. This intercalation not only disrupts the normal function of DNA but also contributes to the cytotoxic effects of these drugs. The combination of inhibiting topoisomerase II and altering DNA shape underscores the powerful mechanism by which anthracyclines can effectively target and kill cancer cells.