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Ching Nung “Selina” Lin, Candidate for Doctor of Pharmacy '25, Massachusetts College of Pharmacy and Health Sciences - Boston
Nancy Yousry, Candidate for Doctor of Pharmacy ‘24, St. John’s University College of Pharmacy and Health Sciences
Chinemerem Opara, Candidate for Doctor of Pharmacy ‘24, The University of North Texas Health Science Center College of Pharmacy
Tiffany Dinh, Candidate for Doctor of Pharmacy ‘24, The University of Texas at Austin College of Pharmacy

Ching Nung “Selina” Lin, Nancy Yousry, and Chinemerem Opara are committee members with the ASHP Pharmacy Student Forum’s (PSF) Advancement of Professional Practice Advisory Group (APPAG). Tiffany Dinh serves as the Chair for the ASHP PSF APPAG.

Ching Nung “Selina” Lin is a third-year pharmacy student from Massachusetts College of Pharmacy- Boston. She is pursuing a Precision Medicine Graduate Certificate, which offers a unique opportunity to delve into pharmacogenomics (PGx). The training equips the students with a deep understanding of drug interactions, patient care, and the clinical implications of genetic variability in drug response. This reflection enables students to bridge the gap between genomic science and its practical application in optimizing patient care and medication management.

BACKGROUND AND HISTORY
The history of pharmacogenomics dates back to 510 B.C. when Pythagoras first invented and discovered its potential. First proposed by English physiologist Archibold Garrod, pharmacogenomics has been found to be cited as enzymatic defects in “inborn errors of metabolism”, but also to the accumulation of exogenously administered substrates including drugs that involve clinical consequences (Kalow, 2005).

Genome-Wide Association Studies (GWAS) have been further developed and conducted on human cohorts and cellular/model organ systems. Biological candidates based on variable pharmacokinetics, pharmacodynamics, and pathway candidate analysis were further studied to identify specific metabolic pathways that influence drug responses. After further identification of the influences of pharmacogenomics on pharmacokinetic and pharmacodynamic responses, variabilities in drug responses were then studied with a precision medicine approach.

In the 1950s, the N-acetylation pathway was discovered as variable and identified as an important contributor to different degrees of isoniazid hepatotoxicity and the lupus syndrome during treatment with procainamide and hydralazine. Varied pharmacokinetic and pharmacodynamic responses were also found to be different and influenced based on ancestry and different places in the world. For instance, the incidence of functionally-important CYP alleles can vary strikingly by ancestry. Poor metabolizers with absent CYP2D6 function are found to be in 5 to 10% of European and African populations but less common for Asian subjects. In comparison, CYP2C19 poor metabolizers are more common in Asian subjects (Roden et al., 2011).

UNDERSTANDING PHARMACOGENOMICS
Understanding pharmacogenomics is crucial for optimizing drug therapy and improving patient outcomes. A fundamental aspect of pharmacogenomics involves genetic variations, which can significantly influence drug metabolism and response. These variations occur in key genes and enzymes that play crucial roles in drug metabolism pathways, such as the cytochrome P450 (CYP) enzymes and drug transporter proteins (CDC, 2022). For instance, single nucleotide polymorphisms (SNPs) in CYP genes can result in altered enzyme activity, affecting the rate at which drugs are metabolized in the body (Adams et al., 2018). Pharmacogenomic testing, which involves analyzing an individual's genetic makeup to identify such variations, holds immense importance in predicting how a patient will respond to certain medications. By understanding a patient's genetic profile, healthcare providers can personalize treatment plans, selecting the most appropriate drugs and dosages to maximize efficacy while minimizing the risk of adverse reactions (Hockings et al., 2020). Thus, pharmacogenomic testing represents a powerful tool in achieving precision medicine and improving patient care.

CLINICAL APPLICATIONS
Clinical applications of pharmacogenomics offer promising avenues for enhancing patient care and treatment outcomes. One significant application is personalized medicine, where drug therapy is customized based on an individual's genetic makeup. By considering genetic variations that impact drug metabolism and response, healthcare providers can prescribe medications that are more likely to be effective and well-tolerated by specific patients (Adams et al., 2018). This tailored approach not only maximizes therapeutic benefits but also minimizes the risk of adverse drug reactions, which is another key advantage of pharmacogenomic testing (Kabbani et al., 2023). Identifying genetic factors that predispose patients to adverse reactions enables proactive measures to prevent such outcomes, ultimately improving patient safety and satisfaction (Hockings et al., 2020). Moreover, pharmacogenomic-guided therapy has the potential to enhance drug efficacy by optimizing dosages and treatment regimens tailored to each patient's genetic profile, leading to better treatment outcomes and overall healthcare quality (Hockings et al., 2020). Therefore, the clinical applications of pharmacogenomics hold immense promise in revolutionizing the practice of medicine towards a more personalized and effective approach to patient care.

CHALLENGES AND LIMITATIONS
Despite its potential benefits, pharmacogenomics also faces several challenges and limitations that need to be addressed for widespread implementation and adoption. One significant challenge is the accessibility and affordability of pharmacogenomic testing (Nicholson et al., 2021). While the cost of genetic testing has decreased over time, it may still be prohibitively expensive for some patients or healthcare systems, limiting widespread access to these valuable tools. Additionally, the interpretation of genetic data obtained from pharmacogenomic testing poses another challenge (Nicholson et al., 2021). Genetic variations can be complex, and translating this information into actionable clinical decisions requires expertise and resources. Healthcare providers may require additional training and support to effectively incorporate genetic data into their decision-making processes (Nicholson et al., 2021). Furthermore, ethical considerations surrounding genetic testing and privacy issues are important to consider (Gershon et al., 2014). Patients may have concerns about the confidentiality and potential misuse of their genetic information, necessitating strong privacy protections and informed consent procedures (Gershon et al., 2014). Addressing these challenges will be essential for realizing the full potential of pharmacogenomics in improving patient care while ensuring equitable access and ethical use of genetic information.

FUTURE DIRECTIONS
The future of pharmacogenomics holds promise for transformative advancements driven by ongoing technological innovations and research endeavors. Advancements in technologies such as next-generation sequencing, microarray analysis, and bioinformatics tools are expected to enhance the efficiency and accuracy of pharmacogenomic testing, facilitating broader implementation and accessibility (Tafazoli, et al., 2021). Furthermore, ongoing research efforts aimed at explaining the relationship between genetics, drug metabolism, and treatment outcomes will continue to expand the understanding of pharmacogenomics, uncovering new biomarkers and therapeutic targets (Tafazoli, et al., 2021). As pharmacogenomic knowledge becomes increasingly integrated into clinical practice, the next frontier lies
in the integration of pharmacogenomic testing into routine patient care pathways (Becquemont, 2009). Efforts to standardize testing protocols, develop clinical decision support systems, and provide education and training to healthcare professionals will be crucial for realizing this vision.

CASE STUDIES
Case studies illustrate the tangible impact of pharmacogenomic testing on patient care and personalized medicine. In oncology, pharmacogenomic testing has been instrumental in guiding treatment decisions by identifying genetic mutations that influence drug response and resistance (Kabbani et al., 2023). The relationship of TPMT, NUDT15 and thiopurines for example, plays an important role to evaluate the therapy decision for patients (CPIC, 2019). Success stories abound, with patients experiencing improved treatment outcomes and quality of life through targeted therapies tailored to their genetic profiles (Kabbani et al., 2023). However, implementing pharmacogenomics in practice is not without its challenges. Issues such as integrating genetic data into electronic health records, ensuring timely access to testing, and educating healthcare providers and patients about the implications of genetic testing require careful consideration (Giri et al., 2018; Moyer et al., 2017). Nevertheless, these challenges offer valuable lessons for refining pharmacogenomic testing protocols, enhancing clinical decision-making processes, and overcoming barriers to implementation.

RACIAL FACTORS IN GENOTYPE
Race and ethnicity serve as valuable factors in informing precision public health initiatives and treatment strategies. For instance, in 2015, following World Health Organization recommendations, Zimbabwe transitioned from three-drug cocktail strategies to efavirenz for HIV treatment (Chimbetete, 2020). However, this change led to many adverse effects like hallucinations, depression, and suicidal tendencies. Subsequently, it was discovered that approximately 20% of the Zimbabwean population experienced adverse events due to possessing two copies of the efavirenz-sensitive genotype (Park, 2023). Another example involves the pharmacogenomic variant CYP3A4 gene, which has been linked to adverse reactions to methadone. The prevalence of the toxic allele is notably higher among Black patients (0.73) compared to White patients. Predictive modeling indicates that the dominant effect mode forecasts adverse events among Black patients at a rate of 723 per 1000 patients, which is the highest among racial groups (Wong et al., 2022). Similarly, the Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) gene variant is more prevalent among Asian patients (0.63) compared to White patients (0.34). According to dominant effect mode predictions, there could be 327 excess adverse drug reactions per 1000 Asian patients due to this genetic variation (Mollan et al., 2017).

STUDENTS’ PERSPECTIVE ON PHARMACOGENOMICS
From a student's perspective, pharmacogenomics offers a captivating journey into the realm where genetics unites with medicine, creating personalized approaches to treatment. Ching Nung “Selina” Lin is enrolled in the Precision Medicine Graduate Program at her school, and it provides a unique opportunity to delve deep into genetic makeup and witness how it influences response to medications. The process of undergoing genetic testing and utilizing the results as a guide throughout the course not only fosters a deeper understanding of pharmacogenomics but also empowers students to navigate their own healthcare. Engaging in debates surrounding genetic topics within the class also enriches their learning experience, allowing them to critically analyze different perspectives and advancements in the field. Moreover, having the autonomy to choose elective courses on pharmacogenomics further tailors students’ academic journey, enabling them to explore specific areas of interest and contribute meaningfully to the discourse surrounding personalized medicine. Overall, from the students’ viewpoint, pharmacogenomics education helps to navigate future implementations and understand the impacts on both personal growth and professional practice.

CONCLUSION
In conclusion, pharmacogenomics stands as a critical field within pharmacy, offering a shift towards personalized medicine and optimized patient care. The significance of pharmacogenomics lies in its ability to tailor drug therapy based on individual genetic makeup, thereby maximizing treatment efficacy while minimizing adverse reactions. Looking ahead, there is a pressing need for further research and widespread adoption of pharmacogenomic testing in clinical practice. Through addressing the current barriers to access, this call to action involves continued investment in technological advancements, education for healthcare providers, and advocacy for policies that support equitable access to genetic testing. By embracing pharmacogenomics, students have the potential to revolutionize healthcare delivery, ushering in an era where treatment decisions are guided by precise genetic insights, ultimately leading to improved health outcomes and enhanced quality of life for patients worldwide.

References:

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