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Review
. 2018 Nov 6;19(11):3480.
doi: 10.3390/ijms19113480.

Anthracyclines as Topoisomerase II Poisons: From Early Studies to New Perspectives

Jessica Marinello  1 , Maria Delcuratolo  2 , Giovanni Capranico  3
Affiliations
Review

Anthracyclines as Topoisomerase II Poisons: From Early Studies to New Perspectives

Jessica Marinello et al. Int J Mol Sci. .

Abstract

Mammalian DNA topoisomerases II are targets of anticancer anthracyclines that act by stabilizing enzyme-DNA complexes wherein DNA strands are cut and covalently linked to the protein. This molecular mechanism is the molecular basis of anthracycline anticancer activity as well as the toxic effects such as cardiomyopathy and induction of secondary cancers. Even though anthracyclines have been used in the clinic for more than 50 years for solid and blood cancers, the search of breakthrough analogs has substantially failed. The recent developments of personalized medicine, availability of individual genomic information, and immune therapy are expected to change significantly human cancer therapy. Here, we discuss the knowledge of anthracyclines as Topoisomerase II poisons, their molecular and cellular effects and toxicity along with current efforts to improve the therapeutic index. Then, we discuss the contribution of the immune system in the anticancer activity of anthracyclines, and the need to increase our knowledge of molecular mechanisms connecting the drug targets to the immune stimulatory pathways in cancer cells. We propose that the complete definition of the molecular interaction of anthracyclines with the immune system may open up more effective and safer ways to treat patients with these drugs.

Keywords: DNA damage; anthracyclines; immunogenic cell death; topoisomerase II; toxic effects.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of the most clinically-used anthracyclines.
See this image and copyright information in PMC

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