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

Drug Discov Ther. 2012 Oct;6(5):230-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drug Design
  • Humans
  • Isoenzymes
  • Molecular Structure
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Poly-ADP-Ribose Binding Proteins
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / pharmacology
  • Topoisomerase II Inhibitors / therapeutic use*


  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Isoenzymes
  • Poly-ADP-Ribose Binding Proteins
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II
  • TOP2A protein, human