Pharmacogenomics, once hailed as a futuristic approach to pharmacotherapy, has transitioned to clinical implementation. Although logistic and economic limitations to clinical pharmacogenomics are being superseded by external measures such as preemptive genotyping, implementation by clinicians has met resistance, partly due to a lack of education. Pharmacists, with extensive training in pharmacology and pharmacotherapy and accessibility to patients, are ideally suited to champion clinical pharmacogenomics. This study aimed to analyze the outcomes of an innovative pharmacogenomic teaching approach. Second-year student pharmacists enrolled in a required, 15-week pharmaceutical care lab course in 2015 completed educational activities including lectures and small group work focusing on practical pharmacogenomics. Reflecting the current landscape of direct-to-consumer (DTC) genomic testing, students were offered 23andMe genotyping. Students completed surveys regarding their attitudes and confidence on pharmacogenomics prior to and following the educational intervention. Paired pre- and post-intervention responses were analyzed with McNemar's test for binary comparisons and the Wilcoxon signed-rank test for Likert items. Responses between genotyped and non-genotyped students were analyzed with Fisher's exact test for binary comparisons and the Mann-Whitney U-test for Likert items. Responses were analyzed for all student pharmacists who voluntarily completed the pre-intervention survey (N = 121, 83% response) and for student pharmacists who completed both pre- and post-intervention surveys (N = 39, 27% response). Of those who completed both pre- and post-intervention surveys, 59% obtained genotyping. Student pharmacists demonstrated a significant increase in their knowledge of pharmacogenomic resources (17.9 vs. 56.4%, p < 0.0001) and confidence in applying pharmacogenomic information to manage patients' drug therapy (28.2 vs. 48.7%, p = 0.01), particularly if the student had received genotyping. Student pharmacists understanding of the risks and benefits of using personal genome testing services significantly increased (55.3 vs. 86.8%, p = 0.001) along with agreement that personal genomics would likely play an important role in their future career (47.4 vs. 76.3%, p = 0.01), particularly among students who participated in genotyping. The educational intervention, including personal genotyping, was feasible, and positively enhanced students' reflections, and attitudes toward pharmacogenomics in a professional pharmacy program.

Pharmacogenomics provides a personalized approach to pharmacotherapy by using genetic information to guide drug dosing and selection. However, partly due to lack of education, pharmacogenomic testing has not been fully implemented in clinical practice. With pharmacotherapy training and patient accessibility, pharmacists are ideally suited to apply pharmacogenomics to patient care. Student pharmacists (n = 222) participated in an educational intervention that included voluntary personal genotyping using 23andMe. Of these, 31% of students completed both pre- and post-educational interventions to evaluate their attitudes and confidence towards the use of pharmacogenomics data in clinical decision making, and 55% of this paired subset obtained personal genotyping. McNemar’s test and the Wilcoxon signed-rank test were used to analyze responses. Following the educational intervention, students regardless of genotyping were more likely to recommend personal genotyping (36% post-educational intervention versus 19% pre-educational intervention, p = 0.0032), more confident in using pharmacogenomics in the management of drug therapy (51% post-educational intervention versus 29% pre-educational intervention, p = 0.0045), and more likely to believe that personalized genomics would have an important role in their future pharmacy career (90% post-educational intervention versus 51% pre-educational intervention, p = 0.0072) compared to before receiving the educational intervention. This educational intervention positively influenced students’ attitudes and confidence regarding pharmacogenomics in the clinical setting. Future studies will examine the use of next-generation sequencing assays that selectively examine pharmacogenes in the education of student pharmacists.

Background: Interpatient variability in immune and chemotherapeutic cytotoxic responses is likely due to complex genetic differences and is difficult to ascertain in humans. Through the use of a panel of genetically diverse mouse inbred strains, we developed a drug screening platform aimed at examining interstrain differences in viability on normal, noncancerous immune cells following chemotherapeutic cytotoxic insult. Drug effects were investigated by comparing selective chemotherapeutic agents, such as BEZ-235 and selumetinib, against conventional cytotoxic agents targeting multiple pathways, including doxorubicin and idarubicin. Methods: Splenocytes were isolated from 36 isogenic strains of mice using standard procedures. Of note, the splenocytes were not stimulated to avoid attributing responses to pathways involved with cellular stimulation rather than toxicity. Cells were incubated with compounds on a nine-point logarithmic dosing scale ranging from 15 nM to 100 µM (37°C, 5% CO₂). At 4 hours posttreatment, cells were labeled with antibodies and physiological indicator dyes and fixed with 4% paraformaldehyde. Cellular phenotypes (eg, viability) were collected and analyzed using flow cytometry. Dose-response curves with response normalized to the zero dose as a function of log concentration were generated using GraphPad Prism 6. Results: Phenotypes were quantified using flow cytometry, yielding interstrain variation for measured endpoints in different immune cells. The flow cytometry assays produced over 16,000 data points that were used to generate dose-response curves. The more targeted agents, BEZ-235 and selumetinib, were less toxic to immune cells than the anthracycline agents. The calculated heritability for the viability of immune cells was higher with anthracyclines than the novel agents, making them better suited for downstream genetic analysis. Conclusion: Using this approach, we identify cell lines of variable sensitivity to chemotherapeutic agents and aim to identify robust, replicable endpoints of cellular response to drugs that provide the starting point for identifying candidate genes and cellular toxicity pathways for future validation in human studies.

The role of the immune system in response to chemotherapeutic agents remains elusive. The interpatient variability observed in immune and chemotherapeutic cytotoxic responses is likely, at least in part, due to complex genetic differences. Through the use of a panel of genetically diverse mouse inbred strains, we developed a drug screening platform aimed at identifying genes underlying these chemotherapeutic cytotoxic effects on immune cells. Using genome-wide association studies (GWAS), we identified four genome-wide significant quantitative trait loci (QTL) that contributed to the sensitivity of doxorubicin and idarubicin in immune cells. Of particular interest, a locus on chromosome 16 was significantly associated with cell viability following idarubicin administration (p = 5.01x10-8). Within this QTL lies App, which encodes amyloid beta precursor protein. Comparison of dose-response curves verified that T-cells in App knockout mice were more sensitive to idarubicin than those of C57BL/6J control mice (p < 0.05). In conclusion, the cellular screening approach coupled with GWAS led to the identification and subsequent validation of a gene involved in T-cell viability after idarubicin treatment. Previous studies have suggested a role for App in in vitro and in vivo cytotoxicity to anticancer agents; the overexpression of App enhances resistance, while the knockdown of this gene is deleterious to cell viability. Thus, further investigations should include performing mechanistic studies, validating additional genes from the GWAS, including Ppfia1 and Ppfibp1, and ultimately translating the findings to in vivo and human studies.