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Editorial
Genome-guided treatment, also known as pharmacogenomics (PGx), may be considered low-hanging fruit in the personalized medicine tree. With the advent of high-throughput genotyping applications and adjacent bioinformatics solutions (Pandi et al. 2021), it holds promise to revolutionize modern medicine, ensuring more individualized prescribing practices to improve efficacy and safety and patients’ quality of life, while contributing to an overall reduction of healthcare expenditure. Even after almost 50 years that the term “pharmacogenetics” was conceived, the field is still rapidly evolving, especially with respect to clinical applications, despite numerous bottlenecks that currently exist and hold back the field (Kampourakis et al. 2014). The various PGx applications and drug–gene correlations have been exhaustively covered and reviewed previously. In this thematic article collection, we have tried to include emerging topics, namely population PGx and genetic diversity, challenges and opportunities in PGx implementation, application of PGx in the developing world, and lastly the impact of PGx in the industry.
Despite the increasing PGx clinical applications in the developed world, such as the United States and North-Western European countries, the field remains poorly developed in developing countries and low resource environments. In their article, El Shamieh and Zgheib (2022) outline the existing gap in research and clinical applications of PGx in the developing world, in terms of inadequate human capital, infrastructure, and research output among others. Not surprisingly, PGx implementation in the clinic has been progressing at a much slower pace. To address these gaps, the authors propose fostering regional and multinational collaborations to resolve issues such as PGx education and training, local and regional capacity building that would allow PGx clinical implementation while preserving individual countries’ identity.
It is well known that drug efficacy and toxicity is dependent upon the ethnogeographic background of the patient, a discipline also known as population PGx (Mette et al. 2012). There are several projects that have attempted to touch upon this topic in various regions, such as Latin America (Bonifaz-Peña et al. 2014), Europe (Mizzi et al. 2016), Middle East (Al-Mahayri et al. 2020) and Asia (Runcharoen et al. 2021). This variability is derived from the differences in PGx biomarkers, dictating mapping and documentation of these biomarkers’ prevalences in various populations, rather than broad races, to optimize population-stratified care (Giardine et al. 2021). In their article, Zhou and Lauschke (2022) provide an extensive updated analysis of population PGx in 10 clinically actionable pharmacogenes, involved in pharmacokinetics, (CYP2D6, CYP2C19, DPYD, TPMT, NUDT15 and SLC22A1), pharmacodynamics (CFTR) and genes involved in drug hypersensitivity (HLA-A, HLA-B) and drug-induced acute hemolytic anemia (G6PD) that affect the pharmacology, efficacy or safety of 141 different drug regimens. The authors report significant differences in the prevalence of these PGx biomarkers among several ethnogeographic groups, providing a solid basis for establishing population-specific genotyping strategies and at the same time informing cost-effectiveness modeling of optimizing provision of personalized therapy interventions towards improved population health.
While there have been many PGx clinical implementation studies worldwide, major challenges exist for more widespread adoption. Tsermpini and coworkers (2022) have meticulously outlined these projects worldwide and provide details of the various study designs, medical specialties that are involved, numbers of patients recruited, and the various study outcomes. The vast majority of these studies indicate that PGx indeed holds promise for improving patients’ health in terms of drug efficacy and toxicity, as well as in their overall quality of life, while simultaneously can contribute to decreases in healthcare expenditure.
Apart from academic clinical and research centers and health care systems, the pharmaceutical industry is becoming increasingly involved in PGx and are utilizing genomic data for the identification of drug targets and the development of personalized medicine approaches. Still, PGx studies are poorly implemented in clinical trials, mostly due to the need to (a) adapt to a constantly changing global regulatory environment, (b) establish the proper study design, and (c) address increasing concerns over patient privacy. In their article, Bienfait and coworkers (2022) describe the establishment of the Industry Pharmacogenomics Working Group (I-PWG), which consists of an association of pharmaceutical companies actively engaged in PGx. The I-PWG, similar to the existing PGx Working Groups of major regulatory bodies, such as the United States Food and Drug Administration, the European Medicines Agency, the Dutch Medicines Authority and others, strive to provide policies and guidelines that pharmaceutical companies should consider to capitalize on scientific and drug development opportunities from PGx.
It is expected that in the years to come, PGx applications will be more broadly applicable in many more areas worldwide, so that a much large proportion of the population worldwide can benefit from drug treatment individualization.
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Acknowledgements
GPP is Full Member and National Representative of the European Medicines Agency, Committee of Human Medicinal Products (CHMP) – Pharmacogenomics Working Party, Amsterdam, the Netherlands. ARS is an employee of Regeneron Pharmaceuticals and receives compensation in the form of salary, stock and stock options.
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GPP is Full Member and National Representative of the European Medicines Agency, Committee of Human Medicinal Products (CHMP) – Pharmacogenomics Working Party, Amsterdam, the Netherlands.
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Patrinos, G.P., Shuldiner, A.R. Pharmacogenomics: the low-hanging fruit in the personalized medicine tree. Hum Genet 141, 1109–1111 (2022). https://doi.org/10.1007/s00439-022-02456-7
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DOI: https://doi.org/10.1007/s00439-022-02456-7