Emerging DNA topisomerase inhibitors as anticancer drugs

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Topoisomerase (topo) enzyme inhibitors are fundamental in cancer chemotherapy.
• Established agents face challenges like limited lactone stability (topo I) and cardiotoxicity (topo II), alongside cellular efflux mechanisms.
• New structural classes of topo inhibitors are actively being explored and developed.

Purpose of the Study:

• To review current and emerging topoisomerase inhibitors in clinical development.
• To highlight efforts in overcoming limitations of existing chemotherapy agents.
• To explore the potential of novel drug design approaches in cancer therapy.

Main Methods:

• Comprehensive review of 24 drugs in various clinical development stages.
• Analysis of established and novel topoisomerase I, topoisomerase II, and dual inhibitors.
• Examination of strategies to improve drug efficacy and reduce toxicity.

Main Results:

• The review encompasses 6 topo I inhibitors, 12 topo II inhibitors, and 6 dual topo I/II inhibitors.
• Significant efforts are directed towards enhancing lactone stability and reducing cardiotoxicity.
• Strategies to counteract cell efflux mechanisms are under investigation.

Conclusions:

• The field of topoisomerase inhibitors remains vigorous, with ongoing development of new agents.
• Dual topo I/II inhibitors represent a promising area, despite early-stage development and limited structural data.
• This research holds potential for innovative drug design strategies in oncology.