Cardiotoxicity of the new cancer therapeutics--mechanisms of, and approaches to, the problem.
Cardiotoxicity of some targeted therapeutics, including monoclonal antibodies and small-molecule inhibitors, is a reality. Herein we will examine why it occurs, focusing on molecular mechanisms to better understand the issue. We will also examine how big the problem is and, more importantly, how big it may become in the future. We will review models for detecting cardiotoxicity in the preclinical phase. We will also focus on two key areas that drive cardiotoxicity: multitargeting and the inherent lack of selectivity of ATP-competitive antagonists. Finally, we will examine the issue of reversibility and discuss possible approaches to keeping patients on therapy.
Force
Thomas
T
Center for Translational Medicine, Jefferson Medical College, 1025 Walnut Street, Philadelphia, PA 19107, USA. thomas.force@jefferson.edu
Kerkelä
Risto
R
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006331:Heart Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents