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Pharmacogenomics review

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https://www.readbyqxmd.com/read/29455673/kinase-targeted-cancer-therapies-progress-challenges-and-future-directions
#1
REVIEW
Khushwant S Bhullar, Naiara Orrego Lagarón, Eileen M McGowan, Indu Parmar, Amitabh Jha, Basil P Hubbard, H P Vasantha Rupasinghe
The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29435777/clinical-review-of-the-pharmacogenomics-of-direct-oral-anticoagulants
#2
REVIEW
Andrew S Tseng, Reema D Patel, Heidi E Quist, Adrijana Kekic, Jacob T Maddux, Christopher B Grilli, Fadi E Shamoun
PURPOSE: There is growing interest in the use of pharmacogenomics to optimize the safety and efficacy of anticoagulation therapy. While the pharmacogenomics of warfarin have been well-studied, the pharmacogenomics of direct oral anticoagulants (DOACs) continue to be a fledgling, but growing, field of interest. We present a pertinent clinical review of the present state of research on the pharmacogenomics of DOACs. METHODS AND RESULTS: The present article is a review of pertinent clinical and scientific research on the pharmacogenomics of DOACs between January 2008 and December 2017 using MEDLINE and the United States National Institutes of Health Clinical Trials Registry...
February 13, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29386902/update-on-subcutaneous-methotrexate-for-inflammatory-arthritis-and-psoriasis
#3
REVIEW
Gino Antonio Vena, Nicoletta Cassano, Florenzo Iannone
Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially rheumatoid arthritis (RA) and moderate-to-severe psoriasis. Oral MTX has been used for the treatment of such diseases for decades for many reasons. There is, however, a relevant interpatient variability of clinical and safety outcomes that can also be related to differences in patients' individual pharmacogenomic profile. Orally administered MTX has been found to have a saturable intestinal absorption and nonlinear pharmacokinetics, with significant consequences on drug bioavailability and clinical efficacy...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29385765/pharmacogenomic-impact-of-cyp2c19-variation-on-clopidogrel-therapy-in-precision-cardiovascular-medicine
#4
REVIEW
Sherry-Ann Brown, Naveen Pereira
Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19. Loss-of-function and gain-of-function variants help explain these interindividual differences. Individuals may carry multiple variants, with linkage disequilibrium noted among some alleles. In the current pharmacogenomics era, genomic variation in CYP2C19 has led to the definition of pharmacokinetic phenotypes for response to antiplatelet therapy, in particular, clopidogrel...
January 30, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29373992/beyond-genomics-understanding-exposotypes-through-metabolomics
#5
REVIEW
Nicholas J W Rattray, Nicole C Deziel, Joshua D Wallach, Sajid A Khan, Vasilis Vasiliou, John P A Ioannidis, Caroline H Johnson
BACKGROUND: Over the past 20 years, advances in genomic technology have enabled unparalleled access to the information contained within the human genome. However, the multiple genetic variants associated with various diseases typically account for only a small fraction of the disease risk. This may be due to the multifactorial nature of disease mechanisms, the strong impact of the environment, and the complexity of gene-environment interactions. Metabolomics is the quantification of small molecules produced by metabolic processes within a biological sample...
January 26, 2018: Human Genomics
https://www.readbyqxmd.com/read/29370938/nav1-7-as-a-pharmacogenomic-target-for-pain-moving-toward-precision-medicine
#6
REVIEW
Yang Yang, Malgorzata A Mis, Mark Estacion, Sulayman D Dib-Hajj, Stephen G Waxman
Chronic pain is a global unmet medical need. Most existing treatments are only partially effective or have side effects that limit their use. Rapid progress in elucidating the contribution of specific genes, including those that encode peripheral voltage-gated sodium channels, to the pathobiology of chronic pain suggests that it may be possible to advance pain pharmacotherapy. Focusing on voltage-gated sodium channel NaV1.7 as an example, this article reviews recent progress in developing patient-specific induced pluripotent stem cells (iPSCs) and their differentiation into sensory neurons, together with advances in structural modeling, that have provided a basis for first-in-human translational studies...
January 19, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29370377/big-data-from-electronic-health-records-for-early-and-late-translational-cardiovascular-research-challenges-and-potential
#7
Harry Hemingway, Folkert W Asselbergs, John Danesh, Richard Dobson, Nikolaos Maniadakis, Aldo Maggioni, Ghislaine Jm van Thiel, Maureen Cronin, Gunnar Brobert, Panos Vardas, Stefan D Anker, Diederick E Grobbee, Spiros Denaxas
Aims: Cohorts of millions of people's health records, whole genome sequencing, imaging, sensor, societal and publicly available data present a rapidly expanding digital trace of health. We aimed to critically review, for the first time, the challenges and potential of big data across early and late stages of translational cardiovascular disease research. Methods and results: We sought exemplars based on literature reviews and expertise across the BigData@Heart Consortium...
August 29, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29356624/from-genomics-to-omics-landscapes-of-parkinson-s-disease-revealing-the-molecular-mechanisms
#8
Sara Redenšek, Vita Dolžan, Tanja Kunej
Molecular mechanisms of Parkinson's disease (PD) have already been investigated in various different omics landscapes. We reviewed the literature about different omics approaches between November 2005 and November 2017 to depict the main pathological pathways for PD development. In total, 107 articles exploring different layers of omics data associated with PD were retrieved. The studies were grouped into 13 omics layers: genomics-DNA level, transcriptomics, epigenomics, proteomics, ncRNomics, interactomics, metabolomics, glycomics, lipidomics, phenomics, environmental omics, pharmacogenomics, and integromics...
January 2018: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/29325731/pharmacogenomic-testing-in-child-and-adolescent-psychiatry-an-evidence-based-review
#9
Anna M Wehry, Laura Ramsey, Shane E Dulemba, Sarah A Mossman, Jeffrey R Strawn
Significant advances have been made in the application of pharmacogenomic testing for the treatment of patients with psychiatric disorders. Over the past decade, a number of studies have evaluated the utility of pharmacogenomic testing in pediatric patients with psychiatric disorders. The evidence base for pharmacogenomic testing in youth with depressive and anxiety disorders as well as attention/deficit hyperactivity disorder (ADHD) is reviewed in this article. General pharmacogenomic principles are summarized and functional polymorphisms in P450 enzymes (and associated metabolizer phenotypes), the serotonin transporter promoter polymorphisms, serotonin 2 A receptor genes (e...
January 8, 2018: Current Problems in Pediatric and Adolescent Health Care
https://www.readbyqxmd.com/read/29286579/systematic-review-of-pharmacogenomics-and-adverse-drug-reactions-in-paediatric-oncology-patients
#10
REVIEW
Rachel Conyers, Subalatha Devaraja, David Elliott
Many paediatric patients with cancer experience significant chemotherapy side effects. Predisposition to drug reactions is governed by single nucleotide polymorphisms (SNPs). We performed a systematic review of the literature from 2006 through 2016. Outcomes of interest included patient characteristics, cancer type drug of interest, genes investigated, toxicity identified and genetic polymorphisms implicated. The primary toxicities studied were neurotoxicity cardiotoxicity, osteonecrosis, and thromboembolism and hypersensitivity reactions...
December 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29283396/pharmacogenomics-of-cyp2c9-functional-and-clinical-considerations
#11
REVIEW
Ann K Daly, Allan E Rettie, Douglas M Fowler, John O Miners
CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions...
December 28, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29283070/pharmacogenomics-of-methotrexate-current-status-and-future-outlook
#12
Mengda Cao, Miao Guo, De-Qin Wu, Ling Meng
BACKGROUND: Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a more efficient, compatible and cost-effective treatment of patients. OBJECTIVE: Present article aims to review genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcome, and try to point out future development directions of individualized MTX therapy...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29283068/influence-of-genetic-polymorphisms-on-mycophenolic-acid-pharmacokinetics-and-patient-outcomes-in-renal-transplantation
#13
Miao Guo, Zi-Jie Wang, Hai-Wei Yang, Ling Meng, Ruo-Yun Tan, Min Gu, Ji-Fu Wei
Mycophenolic acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA, involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and others...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29236081/pharmacogenomics-guided-personalization-of-warfarin-and-tamoxifen
#14
REVIEW
Theodore J Wigle, Laura E Jansen, Wendy A Teft, Richard B Kim
The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date on the association between cytochrome P450 enzymes and the clinical end points of warfarin and tamoxifen therapy. Further, highlighting the clinical experiences that we have gained over the past ten years of running a personalized medicine program, we will offer our perspectives on the utility and the limitations of pharmacogenomics-guided care for warfarin and tamoxifen therapy...
December 13, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29205206/applications-of-pharmacogenomics-in-regulatory-science-a-product-life-cycle-review
#15
W C Tan-Koi, P C Leow, Y Y Teo
With rapid developments of pharmacogenomics (PGx) and regulatory science, it is important to understand the current PGx integration in product life cycle, impact on clinical practice thus far and opportunities ahead. We conducted a cross-sectional review on PGx-related regulatory documents and implementation guidelines in the United States and Europe. Our review found that although PGx-related guidance in both markets span across the entire product life cycle, the scope of implementation guidelines varies across two continents...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29199461/biomarkers-delivering-on-the-expectation-of-molecularly-driven-quantitative-health
#16
Jennifer L Wilson, Russ B Altman
Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29197117/addition-of-allopurinol-for-altering-thiopurine-metabolism-to-optimize-therapy-in-patients-with-inflammatory-bowel-disease
#17
REVIEW
Geoffrey C Wall, Hamid Muktar, Cassandra Effken, Pramod B Mahajan
Thiopurine drugs, including azathioprine and 6-mercaptopurine, are used commonly in patients with inflammatory bowel disease for maintenance of remission. Although generally well tolerated, adverse effects lead to discontinuation in a significant minority of patients. Pharmacogenomic studies have suggested that metabolic breakdown of azathioprine in an individual is genetically determined. Coupled with the fact that certain thiopurine metabolites, notably 6-thioguanine nucleotide and 6-methylmercaptopurine, are associated with antiinflammatory effects and adverse effects, respectively, some investigators have examined intentionally shunting the metabolism of azathioprine toward increasing 6-thioguanine nucleotide levels by using low doses of the xanthine oxidoreductase inhibitor allopurinol to improve efficacy and decrease toxicity of azathioprine in patients with inflammatory bowel disease...
February 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29192598/personalized-medicine-pharmacogenomic-and-companion-biomarker
#18
Hana Manceau, Kawthar Amrani, Katell Peoc'h
The aim of this review is to provide a brief overview of personalized medicine, pharmacogenetics and companion tests. Personalized or stratified medicine is a new paradigm in the management of patients, aimed at better taking into account inter-individual variability. The response to drugs' intake varies considerably, depending on the transport and metabolism of the drugs, the target and the pathophysiological characteristics of the organism. Each stage is very variable and can be modified by endogenous factors (pathophysiology, age, sex, genetics…) or exogenous (environmental: taking other medicines, food, tobacco, alcohol…)...
December 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29186305/systems-bioinformatics-increasing-precision-of-computational-diagnostics-and-therapeutics-through-network-based-approaches
#19
Anastasis Oulas, George Minadakis, Margarita Zachariou, Kleitos Sokratous, Marilena M Bourdakou, George M Spyrou
Systems Bioinformatics is a relatively new approach, which lies in the intersection of systems biology and classical bioinformatics. It focuses on integrating information across different levels using a bottom-up approach as in systems biology with a data-driven top-down approach as in bioinformatics. The advent of omics technologies has provided the stepping-stone for the emergence of Systems Bioinformatics. These technologies provide a spectrum of information ranging from genomics, transcriptomics and proteomics to epigenomics, pharmacogenomics, metagenomics and metabolomics...
November 27, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29181807/pharmacogenomic-biomarkers-for-improved-drug-therapy-recent-progress-and-future-developments
#20
Volker M Lauschke, Lili Milani, Magnus Ingelman-Sundberg
Much of the inter-individual variability in drug efficacy and risk of adverse reactions is due to polymorphisms in genes encoding proteins involved in drug pharmacokinetics and pharmacodynamics or immunological responses. Pharmacogenetic research has identified a multitude of gene-drug response associations, which have resulted in genetically guided treatment and dosing decisions to yield a higher success rate of pharmacological treatment. The rapid technological developments for genetic analyses reveal that the number of genetic variants with importance for drug action is much higher than previously thought and that a true personalized prediction of drug response requires attention to millions of rare mutations...
November 27, 2017: AAPS Journal
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