Validating the pharmacogenomics of chemotherapy-induced cardiotoxicity: What is missing?

Publication date: Available online 5 September 2016 Source:Pharmacology & Therapeutics Author(s): Tarek Magdy, Brian T. Burmeister, Paul W. Burridge The cardiotoxicity of certain chemotherapeutic agents is now well-established, and has led to the development the field cardio-oncology, increased cardiac screening of cancer patients, and limitation of patients' maximum cumulative chemotherapeutic dose. The effect of chemotherapeutic regimes on the heart largely involves cardiomyocyte death, leading to cardiomyopathy and heart failure, or the induction of arrhythmias. Of these cardiotoxic drugs, those resulting in clinical cardiotoxicity can range from 8 to 26% for doxorubicin, 7–28% for trastuzumab, or 5–30% for paclitaxel. For tyrosine kinase inhibitors, QT prolongation and arrhythmia, ischemia and hypertension has been reported in 2–35% of patients. Furthermore, newly introduced chemotherapeutic agents are commonly used as part of changed combinational regimens with significantly increased cardiotoxicity incidence. It is widely believed that the mechanism of action of these drugs is often independent of their cardiotoxicity, and the basis for why these drugs specifically affect the heart has yet to be established. The genetic rationale for why certain patients experience cardiotoxicity whilst other patients can tolerate high chemotherapy doses has proven highly illusive. This has led to significant genomic efforts using targeted and genome-wide association ...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research