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The AAPS Journal May 2016Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of... (Review)
Review
Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of their relatively high specificity, low off-target effects, and biocompatible metabolism, in addition to legal and logistic advantages. However, their clinical utility is limited, among other things, by their high immunogenic potential and/or variable therapeutic efficacy in different patient populations. Both of these issues, also commonly experienced with small molecule drugs, have been addressed effectively in a number of cases by the successful application of pharmacogenomic tools and approaches. In this introductory article of the special issue, we review the current state of application of pharmacogenomics to BTs and offer suggestions for further expansion of the field.
Topics: Animals; Biological Products; Biological Therapy; Biopharmaceutics; Humans; Pharmacogenetics; Recombinant Proteins
PubMed: 27007601
DOI: 10.1208/s12248-016-9903-4 -
Pharmacogenomics Sep 2002With their ability to provide global views of genome sequence and gene activity, microarrays have emerged as key analytical tools in the field of pharmacogenomics. Vast... (Review)
Review
With their ability to provide global views of genome sequence and gene activity, microarrays have emerged as key analytical tools in the field of pharmacogenomics. Vast amounts of data must be collected and analyzed to meet pharmacogenomics' ambitious goals, ranging from identifying markers that predict individuals' responses to therapy to discovering new drug targets. Microarrays will be instrumental to these efforts because they provide bountiful sources of gene expression and genotypic data. Attesting to their productivity, microarrays have been the central technology used in thousands of peer-reviewed publications and have also become important contributors to many databases including PharmGKB, the Cancer Microarray Database and the database of single nucleotide polymorphisms (dbSNP). Microarrays are also making more focused contributions, however, in helping pursue hypothesis-driven inquiries that extend or complement broad genomic surveys. In addition, their potential as clinical tools is being increasingly recognized. This review identifies some of the varied and changing needs of pharmacogenomics research and discusses the ways in which microarrays are tending to these demands. The technique's strongpoints and limitations are examined, as well as its future potential.
Topics: Gene Expression; Genotype; Humans; Oligonucleotide Array Sequence Analysis; Pharmacogenetics; Phenotype
PubMed: 12223046
DOI: 10.1517/14622416.3.5.589 -
Journal of Pediatric Nursing 2014
Review
Topics: Adolescent; Child; Child, Preschool; Female; Forecasting; Humans; Male; Pediatric Nursing; Pediatrics; Pharmacogenetics; Precision Medicine; Quality Improvement; United States
PubMed: 24880100
DOI: 10.1016/j.pedn.2014.04.005 -
Clinical Cancer Research : An Official... May 2012Many clinical trials of oncology drugs now include at least a consideration of pharmacogenomics, the study of germline or acquired genetic factors governing a drug's... (Review)
Review
Many clinical trials of oncology drugs now include at least a consideration of pharmacogenomics, the study of germline or acquired genetic factors governing a drug's response and toxicity. Besides the potential benefit to patients from the consideration of personalized pharmacogenomic information when making treatment decisions, the incentive is clear for oncology drug developers to incorporate pharmacogenomic factors in the drug development process, because pharmacogenomic biomarkers may allow predictive characterization of subpopulations within a disease that may particularly respond or may allow preidentification of patients at highest risk for adverse events. There is, however, a lack of agreement in actual practice about at what point in the oncology clinical drug development process pharmacogenomic studies should be incorporated. In this article, we examine the recent growth of pharmacogenomics in oncology clinical trials, especially in early-phase studies, and examine several critical questions facing the incorporation of pharmacogenomics in early oncologic drug development. We show that phase II clinical trials, in particular, have a favorable track record for showing positive pharmacogenomic signals, worthy of additional follow-up and validation, and that the phase II setting holds significant promise for potentially accelerating and informing future phase III trials. We conclude that phase II trials offer an ideal "sweet spot" for routine incorporation of pharmacogenomic questions in oncology drug development.
Topics: Antineoplastic Agents; Clinical Trials, Phase II as Topic; Humans; Medical Oncology; Neoplasms; Pharmacogenetics; Randomized Controlled Trials as Topic
PubMed: 22427349
DOI: 10.1158/1078-0432.CCR-11-2445 -
Pharmacological Research Apr 2004Pharmacogenetic studies of drugs used in the treatment of asthma have produced a few examples of reduced response in patients carrying specific genotypes in genes... (Review)
Review
Pharmacogenetic studies of drugs used in the treatment of asthma have produced a few examples of reduced response in patients carrying specific genotypes in genes involved in the action of beta-2 agonists or leukotriene modifiers. Other candidate genes related to these drugs, as well as glucocorticoids, theophilline, anticholinergics, antihistaminics, and drug-metabolizing enzymes, may be proposed. Statistical power and population stratification may be issues of importance in case-control association studies. Future developments include expanded gene knowledge from asthma genetic and genomic studies, the development of new preventive and curative treatments, multiple contemporary genotyping methods for pharmacogenetically important genes in a given individual, and the construction of asthma functional pharmacogenomic profiles. In conclusion, it seems that asthma pharmacogenetic studies need to be replicated in prospective clinical trials in different populations with a large number of subjects being genotyped. It is suggested that large clinical trials which are proposed for asthma drugs experimentation should include a pharmacogenetic study as well.
Topics: Animals; Anti-Asthmatic Agents; Asthma; Humans; Pharmacogenetics
PubMed: 15202513
DOI: 10.1016/j.phrs.2003.04.002 -
Clinical Pharmacology and Therapeutics Jul 2016Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic... (Review)
Review
Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding.
Topics: Academic Medical Centers; Humans; Medically Uninsured; Pharmacogenetics; Poverty; Safety-net Providers; Vulnerable Populations
PubMed: 26850569
DOI: 10.1002/cpt.347 -
Discovery Medicine Jun 2011Heart failure, a major clinical problem affecting millions of people, may be modified by the genetic diversity of the affected individuals. A novel medical approach,... (Review)
Review
Heart failure, a major clinical problem affecting millions of people, may be modified by the genetic diversity of the affected individuals. A novel medical approach, personalized medicine, seeks to use genetic information to "personalize" and improve diagnosis, prevention, and therapy. The personalized management of heart failure involves a large spectrum of potential applications, from diagnostics of monogenic disorders, to prevention and management strategies based on modifier genes, to pharmacogenomics. In rare monogenic disorders causing heart failure, recent guidelines now assist the clinician in molecular diagnostics, genetic counseling, and therapeutic choices. Several lines of evidence suggest that common polymorphic variants of modifier genes can influence the susceptibility to heart failure, and it is expected that more advanced high throughput technologies will allow the discovery of a number of novel modifier genes that could be used for prognostic profiling and development of novel therapeutics. Finally, using pharmacogenomic approaches to affect heart failure management appears very promising. Common genetic variants of beta-adrenergic receptors, alpha-adrenergic receptors, and endothelin receptors among others significantly alter the response to heart failure therapy. This knowledge could be used to personalize and optimize heart failure therapy based on the patient's genetic profile. While the advances in technologies will continue to transition personalized medicine from the research to the clinical setting, physicians and in particular cardiologists need to reshape clinical diagnostics paradigms, learn how to use new genomic information to change management decisions, and provide the patients with appropriate education and management recommendations.
Topics: Heart Failure; Humans; Pharmacogenetics; Precision Medicine
PubMed: 21712021
DOI: No ID Found -
Human Genetics May 2015Understanding the role genes and genetic variants play in clinical treatment response continues to be an active area of research with the goal of common clinical use.... (Review)
Review
Understanding the role genes and genetic variants play in clinical treatment response continues to be an active area of research with the goal of common clinical use. This goal has developed into today's industry of pharmacogenomics, where new drug-gene relationships are discovered and further characterized, published and then curated into national and international resources for use by researchers and clinicians. These efforts have given us insight into what a pharmacogenomic variant is, and how it differs from human disease variants and common polymorphisms. While publications continue to reveal pharmacogenomic relationships between genes and specific classes of drugs, many challenges remain toward the goal of widespread use clinically. First, the clinical guidelines for pharmacogenomic testing are still in their infancy. Second, sequencing technologies are changing rapidly making it somewhat unclear what genetic data will be available to the clinician at the time of care. Finally, what and when to return data to a patient is an area under constant debate. New innovations such as PheWAS approaches and whole genome sequencing studies are enabling a tsunami of new findings. In this review, pharmacogenomic variants, pharmacogenomic resources, interpretation clinical guidelines and challenges, such as WGS approaches, and the impact of pharmacogenomics on drug development and regulatory approval are reviewed.
Topics: Computational Biology; Data Interpretation, Statistical; Databases, Genetic; Databases, Pharmaceutical; Drug Discovery; Genetic Variation; Humans; Pharmacogenetics; Phenotype
PubMed: 25238897
DOI: 10.1007/s00439-014-1484-7 -
PLoS Medicine Aug 2007Pharmacogenomics is one of the first clinical applications of the postgenomic era. It promises personalized medicine rather than the established "one size fits all"... (Review)
Review
Pharmacogenomics is one of the first clinical applications of the postgenomic era. It promises personalized medicine rather than the established "one size fits all" approach to drugs and dosages. The expected reduction in trial and error should ultimately lead to more efficient and safer drug therapy. In recent years, commercially available pharmacogenomic tests have been approved by the Food and Drug Administration (FDA), but their application in patient care remains very limited. More generally, the implementation of pharmacogenomics in routine clinical practice presents significant challenges. This article presents specific clinical examples of such challenges and discusses how obstacles to implementation of pharmacogenomic testing can be addressed.
Topics: Biotechnology; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy; Drug Utilization; Humans; Pharmacogenetics; Polymorphism, Genetic; Practice Guidelines as Topic; Technology, Pharmaceutical; United States; United States Food and Drug Administration
PubMed: 17696640
DOI: 10.1371/journal.pmed.0040209 -
Australian Journal of General Practice Mar 2019Patients respond to medications differently because of variations in theĀ genes that determine medication exposure and medication response.
BACKGROUND
Patients respond to medications differently because of variations in theĀ genes that determine medication exposure and medication response.
OBJECTIVE
The aim of this review is to introduce pharmacogenomic testing and explain how to start using pharmacogenomic tests in general practice.
DISCUSSION
Knowledge of the variants in pharmacogenomics is useful when prescribing a variety of medications. International guidelines have identified at least 15 genes for which testing can inform the prescribing of 30 different medications with good evidence of clinical benefit. Nonetheless, pharmacogenomic tests should not be used as the sole basis for prescribing decisions, and should be considered in the context of other relevant clinical and laboratory features. General practitioners can incorporate pharmacogenomic tests into their clinical practice for patients with medication-related problems or those who are likely to require medications for which pharmacogenomics can provide guidance.
Topics: Aged; Australia; Female; General Practice; Genetic Testing; Humans; Male; Middle Aged; Pharmacogenetics; Precision Medicine
PubMed: 31256470
DOI: 10.31128/AJGP-10-18-4733