Progress in cardiovascular diseases
-
Prog Cardiovasc Dis · Sep 2010
ReviewMechanisms of anthracycline cardiac injury: can we identify strategies for cardioprotection?
Anthracycline antibiotics have saved the lives of many cancer victims in the 50 plus years since their discovery. A major limitation of their use is the dose-limiting cardiotoxicity. Efforts focusing on understanding the biochemical basis for anthracycline cardiac effects have provided several strategies currently in clinical use: limit dose exposure, encapsulate anthracyclines in liposomes to reduce myocardial uptake, administer concurrently with the iron chelator dexrazoxane to reduce free iron-catalyzed reactive oxygen species formation; and modify anthracycline structure in an effort to reduce myocardial toxicity. ⋯ There is now evidence that erbB2 signaling in response to the ligand neuregulin regulates anthracycline uptake into cells via the multidrug-resistance protein. Therefore, up-regulation of cardiac neuregulin signaling may be one strategy to limit myocardial anthracycline injury. Moreover, assessing an individual's risk for anthracycline injury may be improved by having some measure of endogenous activity of this and other myocardial protective signals.
-
Prog Cardiovasc Dis · Sep 2010
ReviewCardiac toxicity from systemic cancer therapy: a comprehensive review.
Cardiovascular toxicity is a potential short- or long-term complication of anticancer therapy. Exposure to chemotherapy medications, primarily the anthracycline class, can lead to potentially irreversible clinically significant cardiac dysfunction. The advent of novel biologic agents, including monoclonal antibodies and tyrosine kinase inhibitors, has revolutionized the treatment of several types of malignancies. ⋯ Given the rate of new drug development designed to fulfill unmet oncologic needs, efforts are needed to promote strategies for cardiac risk detection and management and to avoid unintended consequences potentially impeding development of, regulatory approval for, and patient access to novel therapies. These advances require ongoing research to assess and manage the cardiovascular safety of patients treated with anticancer agents, as well as a well-organized collaboration between oncologists and cardiologists. The aim of this review is to summarize potential cardiovascular toxicities for a range of cancer chemotherapeutics and to review general mechanisms of cardiovascular toxicity for each agent.