Introduction

In 2025, our journal Pharmacogenetics and Pharmacogenomics celebrates a landmark date — a decade since its founding. Created in 2015 in response to the rapid growth of genomic technologies, the journal was conceived as a unique platform for integrating fundamental discoveries in the field of hereditary variability of drug response into everyday clinical practice. Over the past decade, it has exceeded expectations, becoming not just a publication, but a genuine catalyst for scientific dialogue and collaboration between clinical pharmacologists, medical geneticists, bioinformaticians, pharmacists and healthcare organizers. 242 original scientific papers published on our pages are not just a number. Each article became a brick in the foundation of overcoming the very “variability of patients” that William Osler (1849–1919) spoke about with deep understanding back in the 19th century, emphasizing that “there are no diseases in general, there are only diseases of a particular person,” but asserting that “if patients were not so different, medicine could well be a science, not an art” [1]. These works moved us from understanding the problem to developing specific tools for personalizing therapy, and pharmacogenetics is the most promising and closest tool to clinical practice. Pharmacogenetics is a science with deep historical roots dating back to the beginning of the 20th century and even earlier. From the description of the first pharmacogenetic phenomena (hemolytic anemia to antimalarial drugs in congenital glucose-6-phosphate dehydrogenase deficiency, prolonged apnea in "congenital" pseudocholinesterase deficiency, malignant hyperthermia during the use of halogen-containing agents for inhalation anesthesia, etc.) [2], through the emergence of the term "pharmacogenetics" and the discovery in the 1950s of a universal heme-containing monooxygenase (cytochrome P450) in rat liver microsomes [3, 4], to the modern era of evidence-based medicine and high-throughput sequencing, including next-generation, the discipline has come a long way. It has evolved from the description of isolated "pharmacogenetic phenomena" causing adverse drug reactions to a systemic understanding of the complex polygenic nature of the pharmacokinetics and pharmacodynamics of the vast majority of drugs. From the very first issue, our journal's mission has been clearly focused on solving three interconnected and critically important tasks:

A striking example of success on this path was one of the early but landmark publications - the work of Chernov A.A. et al., in which one of the first domestic meta-analyses in the field of pharmacogenetics was conducted, as the most important tool for "increasing" the evidence of the influence of pharmacogenetic markers on clinical outcomes of patients [5]. According to the results of the first meta-analysis of domestic studies of the pharmacogenetics of clopidogrel in Russia, it was found that the presence of the CYP2C19*2 polymorphism significantly increased the risk of cardiovascular death and other complications. Such studies have become a symbol of strengthening the evidence base for the effectiveness and feasibility of introducing pharmacogenetic testing into clinical practice.

However, a decade of progress does not mean a lack of challenges. Despite impressive achievements, the implementation of pharmacogenetics into routine clinical practice in the Russian Federation faces significant systemic barriers:

By its anniversary, the editors not only sum up the results, but also approve an ambitious program for the journal's development for the next decade - until 2035, associated with the implementation of tasks aimed at the widespread introduction of pharmacogenetics into clinical practice in medical organizations in Russia, which should contribute, through increasing the effectiveness and safety of pharmacotherapy, to increasing the expected life expectancy of our people:

It is important that these tasks will be implemented in the newly created scientific Center for Predictive Genetics, Pharmacogenetics and Personalization of Therapy of the world level at the State Scientific Center of the Russian Federation "Russian Scientific Center of Surgery named after Academician B.V. Petrovsky", the main focus of which will be pharmacogenetics and pharmacogenomics, which will actively interact with the Russian Medical Academy of Postgraduate Education and other scientific, educational and medical organizations [6].

Personalized medicine, the core of which is pharmacogenetics and pharmacogenomics, is today on the threshold of a new revolution, and our journal intends to be not just a witness, but an active driver of these transformations. In the coming years, we expect a significant shift in the focus of published research:

The journal's tenth anniversary is, of course, a reason for legitimate pride for our entire team of authors, reviewers and readers. But above all, it is a moment of increased responsibility. Pharmacogenetics has finally ceased to be a beautiful theory or "medicine of the distant future" - it has become a real tool capable of saving lives and improving their quality here and now. However, to fully realize its colossal potential, it is necessary:

Future developments in pharmacogenetics and pharmacogenomics

We predict that pharmacogenetics and pharmacogenomics will cease to be auxiliary tools and will become the basis of clinical practice. If 2003 (the completion of the Human Genome Project) marked the beginning of the genomics era, then 2030 will be the year of its maturity, when a patient’s genetic passport will be as routine an element of a patient’s medical history as a blood type or an ECG [7]. The drivers of this transformation will be a technological explosion (reducing the cost of whole-genome sequencing to ≤5,000 rubles, real-time artificial intelligence algorithms), a regulatory revolution (mandatory predictive testing for key drugs), and a change in the healthcare paradigm — the transition from “disease treatment” to “prediction and prevention of individual risks”. Technological breakthroughs will radically change the landscape. It can be assumed that in the future, a complete rejection of targeted panels in favor of WGS (whole-genome sequencing) as a standard for primary diagnostics is possible. This will be possible due to the reduction in the cost of analysis [8], reduction in the execution time to ≤1 hour (due to nanosecond chips) and deep integration with electronic medical records with automatic generation of therapeutic recommendations [9]. The emergence of a “genetic passport at birth” is expected in 80% of developed countries [10].

Artificial intelligence will evolve from analysis to accurate prediction. Neural networks will appear that predict adverse reactions, taking into account >500 parameters (SNP, DNA methylation, metabolomic markers, epidemiological data). They will provide a forecast of the risk of adverse reactions with an accuracy of ≥95% for drugs with a narrow therapeutic window, such as warfarin or carbamazepine [11]. The introduction of digital pharmaceutical avatars (doubles) — personalized simulators based on patient WGS data, allowing in silico testing of the efficacy and toxicity of drug combinations before their actual administration — will be revolutionary [12].

Isolated genome analysis will finally give way to multi-omic convergence. Integrative models will combine data from pharmacogenomics (DNA), proteomics (proteins), transcriptomics (RNA), metabolomics (metabolites), and microbiome analysis (intestinal flora) [13].

Clinical transformations will affect all areas of clinical medicine. In oncology, the use of NGS panels of ≥500 genes for all solid tumors will become routine. The focus will finally shift from cancer localization to its molecular profile: diagnoses will sound like “ALK-positive carcinoma” instead of “lung cancer” or “BRCA-deficient carcinoma” instead of “ovarian cancer”. The concept of neoadjuvant pharmacogenomic prophylaxis may become widespread –– preventive administration of drugs by carriers of highly penetrant mutations 5-10 years before the potential development of cancer. In psychiatry, pharmacogenetic testing will become mandatory before prescribing psychotropic drugs. In primary health care, we can expect the introduction of pharmacogenetic patient cards, with clinical interpretation being carried out with the participation of a clinical pharmacologist, within the framework of specialized telemedicine centers. Implantable biosensors for continuous monitoring of drug concentrations will become available (for example, methotrexate) with automatic dose adjustment via artificial intelligence algorithms.

Social and ethical challenges will require active solutions. The problem of genetic inequality, when access to pharmacogenetic testing remains limited, will require an initiative to create cheap PCR tests for a limited number of the most clinically significant pharmacogenetic markers with very low cost. Data confidentiality will be guaranteed: a ban on the commercial use of WGS data without the explicit consent of the patient, the right to "genetic oblivion" (complete deletion of data from cloud storage) and the introduction of cryptographic protection of DNA information using quantum encryption. For Russia, three strategies will be key. Ethnopharmacogenetics will be developed, which is necessary for prioritizing the implementation of pharmacogenetic testing in various regions. It is expected that educational programs (specialty, residency, postgraduate studies, advanced training) in the field of clinical pharmacogenetics will be introduced more widely, focusing on the interpretation of pharmacogenetic reports, the basics of bioinformatics and resolving ethical dilemmas.

We assume that in the future, the phrase "standard dose" will disappear from the lexicon of doctors, and each drug prescription will be based on a triad: a lifelong genetic passport (WGS profile), a dynamic phenotype (wearable sensor data) and a prognosis by artificial intelligence (individual risk models). The future lies in integrating pharmacogenetics into comprehensive and large-scale clinical and pharmacological counseling of patients, including using telemedicine.

Conclusion

As Paracelsus wisely noted: "The dose makes the poison of the medicine." We, the heirs of his ideas in the era of genomics, dare to add: "Knowledge of the genome makes the dose a salvation." Ahead of us lies a decade of amazing discoveries and transformations in medicine, and the journal "Pharmacogenetics and Pharmacogenomics" will be a faithful companion and assistant to all who follow this path.

The editors express their deepest gratitude to more than 600 authors from Russia, the CIS countries and far abroad, whose research, ideas and discussions have filled the pages of the journal for 10 years. We address special gratitude to our esteemed reviewers. Your invaluable work, deep expertise, constructive criticism and exceptionally strict selection of manuscripts are the main guarantor of the high scientific level and reliability of the published materials. Your work is invisible to the reader, but it is fundamental to the success of the publication.