International Journal of Personalized Medicine
ISSN: Coming Soon
- Pharmacogenomic approaches used in cardio-oncology
- Mechanisms of drug-induced cardiotoxicity
- Economical and clinical burden of CIC
- Single nucleotide polymorphisms (SNPs) associated with drug-induced cardiotoxicity
- Post-GWAS era in cardio-oncology
- Bioinformatic tools and methods for functional annotation of SNPs
- Data management, storage and exploitation
- Application of RNA-seq in cardio-oncology
- Experimental models used for CIC-associated SNPs mechanistic validation
- Role of CRISP/Cas9 in Pharmacogenomics of cardio-oncology
Welcomes submissions to the thematic concept on 'Pharmacogenomics in Cardio-Oncology: Accomplishment and Pitfalls'.
The cardiotoxicity of certain chemotherapeutic agents is now well-established and has led to the development of the field of cardio-oncology, increased cardiac screening of cancer patients, and limitation of patients' maximum cumulative chemotherapeutic dose. Despite the substantial improvement in cancer care, which has resulted in the increase in 5-year survival rate from 35% in the early 1950s to 70% in 2006–2012, the extensive use of chemotherapeutic agents is concordant with a higher incidence of adverse drug events. ADEs are one of the leading causes of death worldwide. According to the US Food and Drug Administration (FDA) adverse drug events reporting system (FAERS), about 1 million serious (including death) ADEs were reported in 2014 in the USA alone (fda.gov). Cardiotoxicity is a common ADE for multiple anti-cancer agents, constituting a significant clinical and economic burden, resulting in the establishment of the field of cardio-oncology to elucidate this phenomenon.
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 from8 to 26% for doxorubicin, 7–28% for trastuzumab, or 5–30% for paclitaxel. For tyrosine kinase inhibitors, QT prolongation and arrhythmia, ischemia and hypertension have been reported in 2–35% of patients. Furthermore, newly introduced chemotherapeutic agents are commonly used as part of changed combinational regimens with significantly increased incidence of cardiotoxicity. 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.
An individual patient's response to chemotherapy is dependent on the plasma and target site concentration of the anticancer drugs, which are controlled by pharmacokinetics (absorption, distribution, metabolism and excretion, ADME) and pharmacodynamics factors. Inherited polymorphisms in drug metabolizing enzymes and transporters can alter their expression and/or activity, influencing pharmacokinetics. Genetic alterations in target enzymes, transporters, ion channels and receptors may influence drug pharmacodynamics. Thus, a realistic option to improve management and outcome of chemotherapy-induced cardiotoxicity (CIC) is the development of individualized treatment strategies including the use of predictive genetic host factors. Extensive efforts in pharmacogenomics research have been conducted in an attempt to uncover the genetic variants associated with chemotherapy clinical outcome. Pharmacogenomic research has utilized increasingly sophisticated approaches to pinpoint genetic variants associated with drug-induced cardiotoxicity from candidate gene association studies (CGAS) and chip-based genome-wide association studies (GWAS) using tag SNPs, to candidate gene resequencing, expression qualitative trait loci (eQTL) mapping, exome sequencing and whole-genome sequencing (WGS).
Submission Instructions: All submissions will undergo peer review and accepted articles will be published in the International Journal of Personalized Medicine.