Abstract
As many novel cancer therapies continue to emerge, the field of Cardio-Oncology (or onco-cardiology) has become crucial to prevent, monitor and treat cancer therapy-related cardiovascular toxicity. Furthermore, given the narrow therapeutic window of most cancer therapies, drug-drug interactions are prevalent in the cancer population. Consequently, there is an increased risk of affecting drug efficacy or predisposing individual patients to adverse side effects. Here we review the role of cytochrome P450 (CYP450) enzymes in the field of Cardio-Oncology. We highlight the importance of cardiac medications in preventive Cardio-Oncology for high-risk patients or in the management of cardiotoxicities during or following cancer treatment. Common interactions between Oncology and Cardiology drugs are catalogued, emphasizing the impact of differential metabolism of each substrate drug on unpredictable drug bioavailability and consequent inter-individual variability in treatment response or development of cardiovascular toxicity. This inter-individual variability in bioavailability and subsequent response can be further enhanced by genomic variants in CYP450, or by modifications of CYP450 gene, RNA or protein expression or function in various ‘omics’ related to precision medicine. Thus, we advocate for an individualized approach to each patient by a multidisciplinary team with clinical pharmacists evaluating a treatment plan tailored to a practice of precision Cardio-Oncology. This review may increase awareness of these key concepts in the rapidly evolving field of Cardio-Oncology.
Highlights
Cardio-Oncology is an emerging field that sits at the interface of Cardiology and Oncology and has close relationships with primary care specialties
When co-administered with chemotherapeutic agents metabolized by the same pathway, such as doxorubicin, imatinib or ibrutinib, this could lead to increased chemotherapy drug concentration
MiR-27b could be used as a biomarker for therapeutics related to CYP1B1 and miR-34a for CYP3A4 and CYP2C19 in addition to transcription factors and other proteins that indirectly affect cytochrome P450 (CYP450) levels or activity (e.g., aldo-keto reductase 1D1 (AKR1D1) and SLC10A1)
Summary
Cardio-Oncology is an emerging field that sits at the interface of Cardiology and Oncology and has close relationships with primary care specialties. Cardiology drugs are widely used by the general population and by individuals with cancer. We highlight several cytochrome P450 (CYP450) enzymes relevant to Cardio-Oncology (Figure 1). We classify drugs as CYP450 substrates, inducers or inhibitors, with an explanation of the three types of drug-enzyme interaction. Drug-drug interactions between Oncology and Cardiology drugs mediated by CYP450 enzymes are surveyed. We discuss the fact that differential metabolism of each substrate drug in each specific individual can determine bioavailability. Examples from precision Cardio-Oncology are integrated to illustrate that inter-individual bioavailability can be further enhanced by genomic variation in CYP450 enzymes. Some variants enhance enzyme activity, while others do just the opposite Adapted from [1] with permission
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