Antitumor agents targeting DNA and DNA-associated processes are widely used in the treatment of human cancers and produce significant increases in the survival of patients. DNA topoisomerases remain the most significant target of these cytotoxic drugs and constitute a growing family of nuclear enzymes that regulate DNA topology during DNA replication and recombination, DNA transcription, chromosome condensation-decondensation and segregation. Major progress has been attained in recent years in the understanding of the structures of these enzymes and their main cellular functions, hopefully providing new opportunities for pharmacological interventions. New leads and derivatives of known structures have been reported recently, and here they will be discussed highlighting the challenges to find innovative and more effective drugs. Moreover, we will review novel and diverse approaches relevant to the development of new topoisomerase-related therapeutics.
Keywords: topoisomerase, topoisomerase-directed drugs, crystal structures, protein toxins, drug receptor, cancer
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