**1. Introduction**

Cardio-Oncology is an emerging field that sits at the interface of Cardiology and Oncology and has close relationships with primary care specialties. A variety of oncology drugs can injure the cardiovascular system, causing various forms of cardiovascular toxicities. Further, cardiology drugs are widely used by the general population and by individuals with cancer. Many of these drugs are also frequently used for preventive cardioprotection or for the management of cardiotoxicity that has already occurred. In this review, 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 also surveyed. In addition, 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. This helps to determine the level of drug available in the body. Not only genomic variants but also other modifications of the enzyme

gene, RNA or protein, including those due to gene-environment interactions, can alter drug levels and individual response in precision medicine. We hope that this review can assist multidisciplinary teams in Cardio-Oncology with difficult drug-related decisions relevant to metabolism and bioavailability.

**Figure 1.** The pie chart depicts the various P450 isoforms, the percentage of clinically used drugs metabolized by the isoform and factors inducing or inhibiting the respective P450 enzyme, thereby influencing variability. The most important factors influencing variability are in bold, with a vertical arrow indicating increased activity (↑), decreased activity (↓) or both (↑↓). Biologic sex (female (f) or male (m)) and rarely polymorphism (CYP1A2) can be of controversial significance. In total, 248 CYP-related drug metabolism pathways were analyzed (excluding chemicals and endogenous substrates). Used with permission [1].
