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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 -
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 -
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 -
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 -
The Medical Clinics of North America Nov 2019Pharmacogenomics (PGx) is a powerful tool that can predict increased risks of adverse effects and sub-therapeutic response to medications. This article establishes the... (Review)
Review
Pharmacogenomics (PGx) is a powerful tool that can predict increased risks of adverse effects and sub-therapeutic response to medications. This article establishes the core principles necessary for a primary care provider to meaningfully and prudently use PGx testing. Key topics include in which patients PGx testing should be considered, how PGx tests are ordered, how the results are translated into clinical recommendations, and what further advancements are likely in the near future. This will provide clinicians with a foundational knowledge of PGx that can allow incorporation of this tool into their practice or support further personal investigation.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Precision Medicine; Primary Health Care
PubMed: 31582008
DOI: 10.1016/j.mcna.2019.07.002 -
Mayo Clinic Proceedings Jan 2021Many practitioners who have not had pharmacogenomic education are required to apply pharmacogenomics to their practices. Although many aspects of pharmacogenomics are... (Review)
Review
Many practitioners who have not had pharmacogenomic education are required to apply pharmacogenomics to their practices. Although many aspects of pharmacogenomics are similar to traditional concepts of drug-drug interactions, there are some differences. We searched PubMed with the search terms pharmacogenomics and pharmacogenetics (January 1, 2005, through December 31, 2019) and selected articles that supported the application of pharmacogenomics to practice. For inclusion, we gave preference to national and international consortium guidelines for implementation of pharmacogenomics. We discuss special considerations important in the application of pharmacogenomics to assist clinicians with ordering, interpreting, and applying pharmacogenomics in their practices.
Topics: General Practitioners; Genetic Testing; Humans; Pharmacogenetics
PubMed: 33308868
DOI: 10.1016/j.mayocp.2020.03.011 -
Seminars in Hematology Jul 2020Inherited genetic variations may alter drug sensitivity in patients with acute lymphoblastic leukemia, predisposing to adverse treatment side effects. In this review, we... (Review)
Review
Inherited genetic variations may alter drug sensitivity in patients with acute lymphoblastic leukemia, predisposing to adverse treatment side effects. In this review, we discuss evidence from children and young adults with acute lymphoblastic leukemia to review the available pharmacogenomic data with an emphasis on clinically actionable and emerging discoveries, for example, genetic variants in thiopurine methyltransferase and NUDT15 that alter 6-mercaptopurine dosing. We also highlight the need for ongoing pharmacogenomic research to validate the significance of recent findings. Further research in young adults, as well as with novel therapeutics, is needed to provide optimal therapy in future trials.
Topics: Humans; Pharmacogenetics; Precision Medicine; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 33256902
DOI: 10.1053/j.seminhematol.2020.10.001 -
Neuroscience Letters May 2020Neurodegenerative disorders (NDDs)(Alzheimer's disease, Parkinson's disease) represent major problems of health in developed countries, with important psychosocial... (Review)
Review
Neurodegenerative disorders (NDDs)(Alzheimer's disease, Parkinson's disease) represent major problems of health in developed countries, with important psychosocial burden for families and high cost for the society. NDDs share some common pathogenic mechanisms such as age-related decline, multiple genetic defects distributed across the genome, deposits of abnormal proteins in the brain, and diverse environmental risk factors. Patients with NDDs currently receive polypharmacy with a high risk for drug-drug interactions and severe adverse drug events. Pharmacogenomics accounts for 60-90% variability in drug pharmacokinetics and pharmacodynamics. Major determinants of the pharmacogenomic outcome include pathogenic, mechanistic, metabolic, transporter and pleiotropic genes. The expression of these genes is under regulatory control of the epigenetic machinery. Approximately, 80% of the Caucasian population is deficient in the metabolization of drugs due to polymorphisms in metabolic genes; consequently, less than 40% of patients respond appropriately to conventional drugs. The implementation of pharmacogenomic procedures in the clinical practice may help to optimize therapeutics in NDDs.
Topics: Alzheimer Disease; Animals; Antiparkinson Agents; Dopamine Agents; Humans; Parkinson Disease; Pharmacogenetics; Polymorphism, Genetic
PubMed: 30236877
DOI: 10.1016/j.neulet.2018.09.018 -
Clinical and Experimental Pharmacology... Aug 2019Genetic polymorphisms impact biological responses to drugs. Current pharmacogenomics guidelines formulated by different countries, such as the Clinical Pharmacogenetics... (Review)
Review
Genetic polymorphisms impact biological responses to drugs. Current pharmacogenomics guidelines formulated by different countries, such as the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, the Canadian Pharmacogenomics Network for Drug Safety, and the French National Network (Réseau) of Pharmacogenetics, play important roles in clinical practices. However, the standards for these guidelines vary significantly, resulting in differences in recommendations. The present article discusses these differences by head-to-head comparison of the existing pharmacogenomics guidelines and proposes new strategies for their future development.
Topics: Guidelines as Topic; Humans; Pharmacogenetics
PubMed: 31009088
DOI: 10.1111/1440-1681.13097