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In vitro modeling of the structure–activity determinants of anthracycline cardiotoxicity

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Abstract

Doxorubicin and other anthracyclines rank among the most effective anticancer drugs ever developed. Unfortunately, the clinical use of anthracyclines is limited by a dose-related life-threatening cardiotoxicity. Understanding how anthracyclines induce cardiotoxicity is essential to improve their therapeutic index or to identify analogues that retain activity while also inducing less severe cardiac damage. Here, we briefly review the prevailing hypotheses on anthracycline-induced cardiotoxicity. We also attempt to establish cause-and-effect relations between the structure of a given anthracycline and its cardiotoxicity when administered as a single agent or during the course of multiagent chemotherapies. Finally, we discuss how the hypotheses generated by preclinical models eventually translate into phase I–II clinical trials.

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Abbreviations

CHF:

congestive heart failure

CL:

clearance

C max :

plasma maximal concentration

DCT:

docetaxel

DNR(OL):

daunorubicin(ol)

DOX(OL):

doxorubicin(ol)

EPI(OL):

epirubicin(ol)

H2O2 :

hydrogen peroxide

IDA:

idarubicin

LVEF:

left ventricular ejection fraction

O2 −⋅ :

superoxide anion

•OH⋅ :

hydroxyl radical

PTX:

paclitaxel

ROS:

reactive oxygen species

V d :

volume of distribution

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Authors and Affiliations

  1. Department of Drug Sciences and Center of Excellence on Aging, G. d’Annunzio University School of Medicine, Chieti, Italy

    P. Menna, G. Minotti & E. Salvatorelli

  2. Department of Drug Sciences and Center of Excellence on Aging, Ce.S.I., G. d’Annunzio University School of Medicine, room 411, Via dei Vestini, 66013, Chieti, Italy

    P. Menna

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  1. P. Menna
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  2. G. Minotti
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Menna, P., Minotti, G. & Salvatorelli, E. In vitro modeling of the structure–activity determinants of anthracycline cardiotoxicity. Cell Biol Toxicol 23, 49–62 (2007). https://doi.org/10.1007/s10565-006-0143-8

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