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Purpose of Review: Adverse drug reactions (ADRs) are a serious burden and can negatively impact patient quality of life. One of these ADRs, anthracycline-induced cardiotoxicity (ACT), occurs in up to 65% of treated patients and can lead to congestive heart failure. Pharmacogenetic studies have helped to reveal the mechanisms of ACT and, consequently, inform current strategies to prevent ACT in the clinic., Recent Findings: Many pharmacogenetic studies have been conducted for ACT, but few have led to the development of clinical practice guidelines and clinical genetic testing for ACT. This is, in part, because of lack of replication in independent patient cohorts and/or validation of an affected biological pathway. Recent advances in pharmacogenetic studies have been made through the use of novel methods that directly implicate dysregulated genes and perturbed biological pathways in response to anthracycline treatment., Summary: Furthering the understanding of the genetics and altered biological pathways of ACT through these novel methods can inform clinical treatment strategies and enable refinement of current clinical practice guidelines. This can therefore lead to improvement in clinical pharmacogenetic testing for further reduction of the incidence of ACT in pediatric cancer patients taking anthracyclines.

Adverse drug reactions (ADRs) are a major problem in modern medicine, representing up to the fourth-highest cause of mortality. Pharmacogenomic tests are 1 of the most promising methods to tackle the challenge of ADRs. The objective of this study was to analyze the clinical and demographic information of the pan-Canadian active surveillance network, Canadian Pharmacogenomics Network for Drug Safety (CPNDS). Information entered into the database by trained active surveillors between May 15, 2005 and May 9, 2017 was collected and analyzed. Specific data included for analysis were number of ADR reports, reports of drug use without ADRs, date of onset of ADR, suspected drugs, concomitant drugs, and fatal ADR cases. The CPNDS database consisted of 93,974 reports of medication use, including 10,475 reports of ADRs, of which 72.6% occurred in pediatric patients (≤21 years old). Self-reported ancestries were predominantly Europe (38.2%), Canada (9.6%), and East Asia (4.9%). The 5 most frequent ADRs were cutaneous ADRs, peripheral neuropathy, cardiotoxicity, central nervous system toxicity, and ototoxicity. The 5 drugs most commonly suspected to cause ADRs were methotrexate, vincristine, doxorubicin, cisplatin, and L-asparaginase. The CPNDS database is a valuable resource to identify clinical and genomic predictors of ADRs. The database also highlights our candidate ADRs for pharmacogenomic discovery research to identify additional ADR biomarkers. Additionally, the database provides information that can be used for developing strategies to prevent ADRs and raises awareness of ADRs among Canadian healthcare professionals., (© 2018, The American College of Clinical Pharmacology.)