Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms.
Fiche publication
Date publication
juin 2015
Journal
Trends in pharmacological sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Pr COTTIN Yves, Pr VERGELY Catherine
Tous les auteurs :
Rochette L, Guenancia C, Gudjoncik A, Hachet O, Zeller M, Cottin Y, Vergely C
Lien Pubmed
Résumé
Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines (ANTHs) such as doxorubicin (DOX). For several decades cardiotoxicity was almost exclusively associated with ANTHs, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor (EGF) receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2(+) tumors. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging.
Mots clés
Animals, Anthracyclines, adverse effects, Antineoplastic Agents, adverse effects, Cardiotoxicity, Drug Synergism, Humans, Myocytes, Cardiac, drug effects, Oxidative Stress, Trastuzumab, adverse effects
Référence
Trends Pharmacol. Sci.. 2015 Jun;36(6):326-48