-
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 -
Epigenetics Dec 2019Growing evidence suggests that aberrant epigenetic regulation of gene function is strongly related to the genesis of cancer. Unlike genetic mutations, the ability to... (Review)
Review
Growing evidence suggests that aberrant epigenetic regulation of gene function is strongly related to the genesis of cancer. Unlike genetic mutations, the ability to reprogram the epigenetic landscape in the cancer epigenome is one of the most promising target therapies in both treatment and reversibility of drug resistance. Epigenetic alterations in cancer development and progression may be the basis for the individual variation in drug response. Thus, this review focuses on the emerging area of pharmaco(epi)genomics, specifically highlighting epigenetic reprogramming during tumorigenesis and how epigenetic markers are targeted as a therapy (epidrugs) and the clinical implications of this for cancer treatment.
Topics: Animals; Antineoplastic Agents; Epigenesis, Genetic; Epigenomics; Humans; Neoplasms; Pharmacogenetics
PubMed: 31282279
DOI: 10.1080/15592294.2019.1640546 -
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 -
Pharmacogenomics Jan 2023Breast cancer was declared the most prevalent type of cancer in 2020. Among other factors, treatment response can be affected by genetic polymorphisms - which is the... (Review)
Review
Breast cancer was declared the most prevalent type of cancer in 2020. Among other factors, treatment response can be affected by genetic polymorphisms - which is the focus of pharmacogenetics - and ethnicity is also a contributing factor in this context. Relevant genes in disease treatment pathways were selected to evaluate treatment response from the pharmacogenetic perspective; polymorphism frequencies and ethnic and continental representation across the available literature were also assessed through a systematic review. The identified associations and gaps have been described in this study with the purpose that, in the future, treatments can be personalized and thus be more effective, safer, and accessible to all.
Topics: Humans; Female; Breast Neoplasms; Polymorphism, Genetic; Pharmacogenetics; Ethnicity
PubMed: 36475975
DOI: 10.2217/pgs-2022-0144 -
Nature Reviews. Cardiology Sep 2021Over the past decade, pharmacogenetic testing has emerged in clinical practice to guide selected cardiovascular therapies. The most common implementation in practice is... (Review)
Review
Over the past decade, pharmacogenetic testing has emerged in clinical practice to guide selected cardiovascular therapies. The most common implementation in practice is CYP2C19 genotyping to predict clopidogrel response and assist in selecting antiplatelet therapy after percutaneous coronary intervention. Additional examples include genotyping to guide warfarin dosing and statin prescribing. Increasing evidence exists on outcomes with genotype-guided cardiovascular therapies from multiple randomized controlled trials and observational studies. Pharmacogenetic evidence is accumulating for additional cardiovascular medications. However, data for many of these medications are not yet sufficient to support the use of genotyping for drug prescribing. Ultimately, pharmacogenetics might provide a means to individualize drug regimens for complex diseases such as heart failure, in which the treatment armamentarium includes a growing list of medications shown to reduce morbidity and mortality. However, sophisticated analytical approaches are likely to be necessary to dissect the genetic underpinnings of responses to drug combinations. In this Review, we examine the evidence supporting pharmacogenetic testing in cardiovascular medicine, including that available from several clinical trials. In addition, we describe guidelines that support the use of cardiovascular pharmacogenetics, provide examples of clinical implementation of genotype-guided cardiovascular therapies and discuss opportunities for future growth of the field.
Topics: Cardiovascular Agents; Cardiovascular Diseases; Humans; Pharmacogenetics
PubMed: 33953382
DOI: 10.1038/s41569-021-00549-w -
Pharmacogenomics Sep 2021Genetic polymorphism in olanzapine-metabolizing enzymes, transporters and drug targets is associated with alterations in safety and efficacy. The aim of this systematic...
Genetic polymorphism in olanzapine-metabolizing enzymes, transporters and drug targets is associated with alterations in safety and efficacy. The aim of this systematic review is to describe all clinically relevant pharmacogenetic information on olanzapine and to propose clinically actionable variants. Two hundred and eighty-four studies were screened; 76 complied with the inclusion criteria and presented significant associations. Taq1A (rs1800497) *A1, -2548 (rs7799039) G and *1F alleles were related to olanzapine effectiveness and safety variability in several studies, with a high level of evidence. -141 (rs1799732) Ins, A-241G (rs1799978) G, Ser9Gly (rs6280) Gly, rs7997012 A, C3435T (rs1045642) T and G2677T/A (rs2032582) T and *3 alleles were related to safety, effectiveness and/or pharmacokinetic variability with moderated level of evidence.
Topics: Antipsychotic Agents; Humans; Olanzapine; Pharmacogenetics; Polymorphism, Genetic; Schizophrenia; Treatment Outcome
PubMed: 34528455
DOI: 10.2217/pgs-2021-0051 -
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 -
Clinical Pharmacology and Therapeutics Sep 2021The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is... (Review)
Review
The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is highly debated. Therefore, the purpose of this review is to summarize different perspectives on the evidence required for the clinical implementation of pharmacogenetics. First, we present two patient cases that demonstrate how knowledge of pharmacogenetic evidence affected their care. Then we summarize resources that curate pharmacogenetic evidence, types of evidence (with an emphasis on randomized controlled trials [RCT]) and their limitations, and different perspectives from implementers, clinicians, and patients. We compare pharmacogenetics to a historical example (i.e., the evidence required for the clinical implementation of pharmacokinetics/therapeutic drug monitoring), and we provide future perspectives on the evidence for pharmacogenetic panels and the need for more education in addition to evidence. Although there are differences in the interpretation of pharmacogenetic evidence across resources, efforts for standardization are underway. Survey data illustrate the value of pharmacogenetic testing from the patient perspective, with their providers seen as key to ensuring maximum benefit from test results. However, clinicians and practice guidelines from medical societies often rely on RCT data to guide treatment decisions, which are not always feasible or ethical in pharmacogenetics. Thus, recognition of other types of evidence to support pharmacogenetic implementation is needed. Among pharmacogenetic implementers, consistent evidence of pharmacogenetic associations is deemed most critical. Ultimately, moving pharmacogenetics into practice will require consideration of multiple stakeholder perspectives, keeping particularly attuned to the voice of the ultimate stakeholder-the patient.
Topics: Drug Monitoring; Humans; Pharmacogenetics; Reference Standards; Surveys and Questionnaires
PubMed: 34101169
DOI: 10.1002/cpt.2327 -
Journal of the American Academy of... Jun 2021Thank you for the opportunity to respond to the letter, "Thoughtful Clinical Use of Pharmacogenetics in Child and Adolescent Psychopharmacology." We appreciate the...
Thank you for the opportunity to respond to the letter, "Thoughtful Clinical Use of Pharmacogenetics in Child and Adolescent Psychopharmacology." We appreciate the thoughtful consideration by Ramsey et al. of the American Academy of Child and Adolescent Psychiatry (AACAP) policy statement on the Clinical Use of Pharmacogenetic Tests in Prescribing Psychotropic Medications for Children and Adolescents. In this reply, we will highlight many of the important points that the authors have included and will also express our concerns regarding some of the authors' conclusions in light of the current level of evidence.
Topics: Adolescent; Adolescent Psychiatry; Child; Humans; Pharmacogenetics; Psychotropic Drugs; United States
PubMed: 34090655
DOI: 10.1016/j.jaac.2021.04.007 -
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