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Genes Jun 2020Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient's genetic features. In recent years, several...
Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient's genetic features. In recent years, several pharmacogenetic guidelines have been published by international scientific consortia, but the uptake in clinical practice is still poor. Many coordinated international efforts are ongoing in order to overcome the existing barriers to pharmacogenomic implementation. On the other hand, existing validated pharmacogenomic markers can explain only a minor part of the observed clinical variability in the therapeutic outcome. New investigational approaches are warranted, including the study of the pharmacogenomic role of the immune system genetics and of previously neglected rare genetic variants, reported to account for a large part of the inter-individual variability in drug metabolism. In this Special Issue, we collected a series of articles covering many aspects of pharmacogenomics. These include clinical implementation of pharmacogenomics in clinical practice, development of tools or infrastractures to support this process, research of new pharmacogenomics markers to increase drug efficacy and safety, and the impact of rare genetic variants in pharmacogenomics.
Topics: Biomarkers; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 32580376
DOI: 10.3390/genes11060679 -
Lancet (London, England) Aug 2019Genomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. The idea that genetic variation can be... (Review)
Review
Genomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. The idea that genetic variation can be used to individualise drug therapy-the topic addressed here-is often viewed as within reach for genomic medicine. We have reviewed general mechanisms underlying variability in drug action, the role of genetic variation in mediating beneficial and adverse effects through variable drug concentrations (pharmacokinetics) and drug actions (pharmacodynamics), available data from clinical trials, and ongoing efforts to implement pharmacogenetics in clinical practice.
Topics: Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Pharmacogenomic Variants
PubMed: 31395440
DOI: 10.1016/S0140-6736(19)31276-0 -
Advances in Experimental Medicine and... 2019Following the completion of the Human Genome Project in 2003, research in oncology has progressively focused on the sequencing of cancer genomes, with the aim of better... (Review)
Review
Following the completion of the Human Genome Project in 2003, research in oncology has progressively focused on the sequencing of cancer genomes, with the aim of better understanding the genetic basis of oncogenesis and identifying actionable alterations. The development of next-generation-sequencing (NGS) techniques, commercially available since 2006, allowed for a cost- and time-effective sequencing of tumor DNA, leading to a "genomic era" of cancer research and treatment. NGS provided a significant step forward in Personalized Medicine (PM) by enabling the detection of somatic driver mutations, resistance mechanisms, quantification of mutational burden, germline mutations which settled the foundation of a new approach in cancer care. In this chapter we discuss the history, available techniques and applications of NGS in oncology, with a particular referral to the PM approach and the emerging role of the research field of pharmacogenomics.
Topics: High-Throughput Nucleotide Sequencing; Humans; Neoplasms; Pharmacogenetics; Precision Medicine
PubMed: 31713162
DOI: 10.1007/978-3-030-24100-1_2 -
Trends in Pharmacological Sciences Dec 2022Genetic factors can, to a certain extent, successfully predict the therapeutic effects, metabolism, and adverse reactions of drugs. This research field,... (Review)
Review
Genetic factors can, to a certain extent, successfully predict the therapeutic effects, metabolism, and adverse reactions of drugs. This research field, pharmacogenomics, is well developed in oncology and is currently expanding in psychiatry. Here, we summarize the latest development in pharmacogenomic psychiatry, where results of several recent large studies indicate a true benefit and cost-effectiveness of pre-emptive genotyping for more successful psychotherapy. However, it is apparent that we still lack knowledge of many additional heritable genetic factors of importance for explanation of the interindividual differences in response to psychiatric drugs. Thus, more effort to further develop pharmacogenomic psychiatry should be invested to achieve a broader clinical implementation.
Topics: Humans; Pharmacogenetics; Depression; Precision Medicine; Psychotic Disorders; Medical Oncology
PubMed: 36307251
DOI: 10.1016/j.tips.2022.09.011 -
Nature Oct 2015After decades of discovery, inherited variations have been identified in approximately 20 genes that affect about 80 medications and are actionable in the clinic. And... (Review)
Review
After decades of discovery, inherited variations have been identified in approximately 20 genes that affect about 80 medications and are actionable in the clinic. And some somatically acquired genetic variants direct the choice of 'targeted' anticancer drugs for individual patients. Current efforts that focus on the processes required to appropriately act on pharmacogenomic variability in the clinic are moving away from discovery and towards implementation of an evidenced-based strategy for improving the use of medications, thereby providing a cornerstone for precision medicine.
Topics: Evidence-Based Medicine; Genetic Testing; Genetic Variation; Humans; Neoplasms; Pharmacogenetics; Precision Medicine
PubMed: 26469045
DOI: 10.1038/nature15817 -
International Journal of Molecular... Dec 2021Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon... (Review)
Review
Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug-drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.
Topics: Biomarkers; Cardiovascular Diseases; Central Nervous System Diseases; Cost-Benefit Analysis; Drug Development; Drug-Related Side Effects and Adverse Reactions; Genotype; Humans; Neoplasms; Pharmaceutical Preparations; Pharmacogenetics; Phenotype; COVID-19 Drug Treatment
PubMed: 34948113
DOI: 10.3390/ijms222413302 -
Neuroscience Letters May 2020
Topics: Genome-Wide Association Study; Humans; Mental Disorders; Pharmacogenetics; Psychotropic Drugs
PubMed: 31682873
DOI: 10.1016/j.neulet.2019.134602 -
Journal of Pharmacokinetics and... Apr 2019Here we characterize and summarize the pharmacokinetic changes for metabolized drugs when drug-drug interactions and pharmacogenomic variance are observed. Following... (Review)
Review
Here we characterize and summarize the pharmacokinetic changes for metabolized drugs when drug-drug interactions and pharmacogenomic variance are observed. Following multiple dosing to steady-state, oral systemic concentration-time curves appear to follow a one-compartment body model, with a shorter rate limiting half-life, often significantly shorter than the single dose terminal half-life. This simplified disposition model at steady-state allows comparisons of measurable parameters (i.e., area under the curve, half-life, maximum concentration and time to maximum concentration) following drug interaction or pharmacogenomic variant studies to be utilized to characterize whether a drug is low versus high hepatic extraction ratio, even without intravenous dosing. The characteristics of drugs based on the ratios of area under the curve, maximum concentration and half-life are identified with recognition that volume of distribution is essentially unchanged for drug interaction and pharmacogenomic variant studies where only metabolic outcomes are changed and transporters are not significantly involved. Comparison of maximum concentration changes following single dose interaction and pharmacogenomic variance studies may also identify the significance of intestinal first pass changes. The irrelevance of protein binding changes on pharmacodynamic outcomes following oral and intravenous dosing of low hepatic extraction ratio drugs, versus its relevance for high hepatic extraction ratio drugs is re-emphasized.
Topics: Area Under Curve; Drug Interactions; Half-Life; Humans; Metabolic Clearance Rate; Pharmaceutical Preparations; Pharmacogenetics
PubMed: 30911879
DOI: 10.1007/s10928-019-09626-7 -
Pediatric Clinics of North America Oct 2023Pharmacogenomics, where genomic information is used to tailor medication management, is a strategy to maximize drug efficacy and minimize toxicity. Although pediatric... (Review)
Review
Pharmacogenomics, where genomic information is used to tailor medication management, is a strategy to maximize drug efficacy and minimize toxicity. Although pediatric evidence is less robust than for adults, medications influenced by pharmacogenomics are prescribed to children and adolescents. Evidence-based guidelines and drug label annotations are available from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Pharmacogenomics Knowledgebase (PharmGKB). Some pediatric health care facilities use pharmacogenomics to provide dosing recommendations to pediatricians. Herein, we use a case-based approach to illustrate the use of pharmacogenomic data in pediatric clinical care and provide resources for finding and using pharmacogenomic guidelines.
Topics: Adolescent; Adult; Humans; Child; Pharmacogenetics; Pediatricians
PubMed: 37704356
DOI: 10.1016/j.pcl.2023.05.010 -
Genes May 2024Over the last few decades, the implementation of pharmacogenomics (PGx) in clinical practice has improved tailored drug prescriptions [...].
Over the last few decades, the implementation of pharmacogenomics (PGx) in clinical practice has improved tailored drug prescriptions [...].
Topics: Pharmacogenetics; Humans; Precision Medicine
PubMed: 38927650
DOI: 10.3390/genes15060714