Anthracycline cardiotoxicity in breast cancer patients: Synergism with trastuzumab and taxanes

Luca Gianni, Emanuela Salvatorelli, Giorgio Minotti

Research output: Contribution to journalArticle

Abstract

Doxorubicin is known to cause cardiomyopathy and congestive heart failure (CHF) upon chronic administration. A major obstacle to doxorubicin-containing multiagent therapies pertains to the possible development of cardiomyopathy and CHF at lower than expected cumulative doses of doxorubicin. For example, the cardiac toxicity of doxorubicin is aggravated by the anti-HER2 antibody Trastuzumab or by the tubulin-active taxane paclitaxel; however, the mechanisms by which Trastuzumab and paclitaxel aggravate doxorubicin-induced cardiotoxicity are mechanistically distinct: Trastuzumab interferes with cardiac-specific survival factors that help the heart to withstand stressor agents like anthracyclines, while paclitaxel acts by stimulating the formation of anthracycline metabolites that play a key role in the mechanism of cardiac failure. Here, we briefly review the molecular mechanisms of the cardiotoxic synergism of Trastuzumab or paclitaxel with doxorubicin, and we attempt to briefly outline how the mechanistic know-how translates into the clinical strategies for improving the safety of anthracycline-based multiagent therapies.

Original languageEnglish
Pages (from-to)67-71
Number of pages5
JournalCardiovascular Toxicology
Volume7
Issue number2
DOIs
Publication statusPublished - Jun 2007

Fingerprint

Taxoids
Anthracyclines
Doxorubicin
Breast Neoplasms
Paclitaxel
Heart Failure
Cardiomyopathies
Tubulin
Metabolites
Toxicity
Cardiotoxicity
Trastuzumab
Anti-Idiotypic Antibodies
Safety
Survival
Antibodies
Therapeutics

Keywords

  • Anthracyclines
  • Cardiotoxicity
  • Taxanes
  • Toxic synergism
  • Trastuzumab

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Toxicology

Cite this

Anthracycline cardiotoxicity in breast cancer patients : Synergism with trastuzumab and taxanes. / Gianni, Luca; Salvatorelli, Emanuela; Minotti, Giorgio.

In: Cardiovascular Toxicology, Vol. 7, No. 2, 06.2007, p. 67-71.

Research output: Contribution to journalArticle

Gianni, Luca ; Salvatorelli, Emanuela ; Minotti, Giorgio. / Anthracycline cardiotoxicity in breast cancer patients : Synergism with trastuzumab and taxanes. In: Cardiovascular Toxicology. 2007 ; Vol. 7, No. 2. pp. 67-71.
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