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DNA topoisomerase-targeting chemotherapeutics: what's new?

Selma M Cuya1, Mary-Ann Bjornsti1, Robert C A M van Waardenburg2

  • 1Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 155 Volker Hall, 1720 2nd Ave. S., Birmingham, AL, 35294-0019, USA.

Cancer Chemotherapy and Pharmacology
|May 22, 2017
PubMed

Insights

Human cells use DNA topoisomerases to manage DNA topology and integrity. These enzymes, targeted by cancer drugs, are crucial for cellular function and therapeutic development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Human cells possess six DNA topoisomerases (TOP1, TOP1mt, TOP2α, TOP2β, TOP3α, TOP3β) essential for genome and RNA integrity.
  • Topoisomerases regulate DNA supercoiling and resolve topological issues by creating transient DNA breaks.
  • Covalent topoisomerase-DNA complexes are key targets for numerous anticancer chemotherapeutics.

Purpose of the Study:

  • To review the structure-function and catalytic mechanisms of eukaryotic DNA topoisomerase families.
  • To discuss topoisomerase-targeting agents in clinical use or trials.
  • To highlight advancements and challenges in the clinical development of these agents.

Main Methods:

  • Literature review of eukaryotic DNA topoisomerases.
  • Analysis of structure-function and catalytic mechanisms.
  • Review of clinical data for topoisomerase-targeting agents.

Main Results:

  • Detailed overview of type IB, IIA, and IA topoisomerase families.
  • Compilation of approved and investigational topoisomerase-targeting drugs.
  • Identification of current challenges and future directions in clinical development.

Conclusions:

  • DNA topoisomerases are vital for maintaining genomic stability and are validated targets for cancer therapy.
  • Understanding topoisomerase mechanisms informs the development of novel chemotherapeutics.
  • Continued research is necessary to overcome challenges in the clinical application of topoisomerase inhibitors.
Keywords:
Cancer chemotherapeuticsCatalytic mechanismDNA topoisomerasesDNA topology

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