Topoisomerase IIα, rather than IIβ, is a promising target in development of anti-cancer drugs.

DNA topoisomerase II (TOP2) is a well-known anticancer target. Its inhibitors are among the most effective anticancer drugs currently in clinical use. TOP2-targeting agents fall into two major classes of "Topo poisons" and "Topo inhibitors" based on their mechanisms of action. Mammalian cells possess two genetically distinct TOP2 isoforms, TOP2α and TOP2β, that are differentially regulated and play different roles in living cells. Compared to TOP2β, TOP2α may be an efficacious and safe chemotherapeutic target for cancer treatment. This review discusses the advantage of targeting TOP2α over TOP2β and action of various agents on TOP2α.