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Experimental Physiology May 2005There is large interpatient variability in the response to drugs, including cardiovascular drugs. Thus, while some patients achieve the desired therapeutic response from... (Review)
Review
There is large interpatient variability in the response to drugs, including cardiovascular drugs. Thus, while some patients achieve the desired therapeutic response from their drug therapy, others do not. There is also a subset of patients who will experience adverse effects, which can range from bothersome to life threatening. Research in recent years has provided compelling evidence that in many cases, genetics contributes importantly to this variable drug response. Thus, pharmacogenomics is a field focused on unravelling the genetic determinants of variable drug response. Examples from the literature of genetic associations with drug efficacy and toxicity are described to provide insight into the field, including the roles of genetic variability in drug-metabolizing enzymes and drug targets. There is also a detailed discussion of the experimental approaches used in cardiovascular pharmacogenomics. Current research is largely focused on a limited candidate gene approach, which allows for description of significant genetic associations with variable response, but often does not explain the genetic basis of variable drug response enough to be useful clinically. As such, there is a move towards genome-wide approaches, and the various technologies available to obtain genomic data are discussed. Cardiovascular pharmacogenomics has the potential for leading to improvements in the use of cardiovascular drug therapy, through selection of the most appropriate drug therapy in an individual based on their genetic information. It will probably be a decade or more before genetic information is widely used in drug therapy decisions, but it seems clear that important findings in the area will continue to expand and the experimental approaches will continue to evolve.
Topics: Animals; Cardiovascular Diseases; Clinical Trials as Topic; Drug Delivery Systems; Drug Design; Gene Targeting; Genetic Therapy; Genomics; Humans; Pharmacogenetics
PubMed: 15778411
DOI: 10.1113/expphysiol.2004.028506 -
PLoS Computational Biology 2012There is great variation in drug-response phenotypes, and a "one size fits all" paradigm for drug delivery is flawed. Pharmacogenomics is the study of how human genetic...
There is great variation in drug-response phenotypes, and a "one size fits all" paradigm for drug delivery is flawed. Pharmacogenomics is the study of how human genetic information impacts drug response, and it aims to improve efficacy and reduced side effects. In this article, we provide an overview of pharmacogenetics, including pharmacokinetics (PK), pharmacodynamics (PD), gene and pathway interactions, and off-target effects. We describe methods for discovering genetic factors in drug response, including genome-wide association studies (GWAS), expression analysis, and other methods such as chemoinformatics and natural language processing (NLP). We cover the practical applications of pharmacogenomics both in the pharmaceutical industry and in a clinical setting. In drug discovery, pharmacogenomics can be used to aid lead identification, anticipate adverse events, and assist in drug repurposing efforts. Moreover, pharmacogenomic discoveries show promise as important elements of physician decision support. Finally, we consider the ethical, regulatory, and reimbursement challenges that remain for the clinical implementation of pharmacogenomics.
Topics: Drug Discovery; Genome-Wide Association Study; Humans; Pharmacogenetics
PubMed: 23300409
DOI: 10.1371/journal.pcbi.1002817 -
International Journal of Environmental... Aug 2022Pharmacogenomics (PGx) and personalized medicine embrace the potential to optimize drug treatment and improve the patient's quality of life. Pharmacists' roles include...
BACKGROUND
Pharmacogenomics (PGx) and personalized medicine embrace the potential to optimize drug treatment and improve the patient's quality of life. Pharmacists' roles include contributing to genetic testing, patient counseling, and pharmacotherapies selection for superior treatment outcomes. The aim of this study is to assess the pharmacists' knowledge, insight, and self-confidence toward PGx testing, identify their future preferred education patterns, and determine the barriers to pharmacogenomic testing implementation.
METHOD
A cross-sectional study was conducted using a previously validated questionnaire among pharmacists working in the Kingdom of Saudi Arabia (KSA). The questionnaire was designed in seven major categories, consisting of 26 questions.
RESULTS
A total of 671 pharmacists participated in this survey. As for knowledge, only 29.8% of pharmacists had good knowledge regarding PGx, while 42.9% had poor knowledge levels. Respectable PGx knowledge was significantly higher among outpatient dispensing pharmacists (33.6%; = 0.049) and among pharmacists who had completed PGx testing-related training or education (40.3%; = 0.001). Considering perception, it was positive among 50% of pharmacists and negative among 19.8%. With regard to self-confidence, it was high among 39.2% of male pharmacists ( = 0.042), among 43% of clinical pharmacists ( = 0.006), and among 44.8% of pharmacists who had extra credentials ( = 0.001). The utmost favored continuing-education learning approaches were workshops or seminars. The barriers to the implementation of PGx testing included a lack of testing devices, clinical guidelines, training or education, and personnel.
CONCLUSION
The present study revealed that pharmacists in KSA had inadequate knowledge and understanding of PGx. Nevertheless, the majority established that PGx is a valuable tool for augmenting drug efficacy and safety.
Topics: Cross-Sectional Studies; Humans; Male; Pharmacists; Pharmacogenetics; Quality of Life; Saudi Arabia
PubMed: 36011723
DOI: 10.3390/ijerph191610073 -
Genes Apr 2024In recent years, the FDA has approved numerous anti-cancer drugs that are mutation-based for clinical use. These drugs have improved the precision of treatment and... (Review)
Review
In recent years, the FDA has approved numerous anti-cancer drugs that are mutation-based for clinical use. These drugs have improved the precision of treatment and reduced adverse effects and side effects. Personalized therapy is a prominent and hot topic of current medicine and also represents the future direction of development. With the continuous advancements in gene sequencing and high-throughput screening, research and development strategies for personalized clinical drugs have developed rapidly. This review elaborates the recent personalized treatment strategies, which include artificial intelligence, multi-omics analysis, chemical proteomics, and computation-aided drug design. These technologies rely on the molecular classification of diseases, the global signaling network within organisms, and new models for all targets, which significantly support the development of personalized medicine. Meanwhile, we summarize chemical drugs, such as lorlatinib, osimertinib, and other natural products, that deliver personalized therapeutic effects based on genetic mutations. This review also highlights potential challenges in interpreting genetic mutations and combining drugs, while providing new ideas for the development of personalized medicine and pharmacogenomics in cancer study.
Topics: Precision Medicine; Humans; Biological Products; Neoplasms; Antineoplastic Agents; Pharmacogenetics; Mutation
PubMed: 38674402
DOI: 10.3390/genes15040468 -
Genes Mar 2021Since the term "pharmacogenetics" was first published in the late 1950s by Friedrich Vogel, the field has evolved into genome-wide association studies identifying novel...
Since the term "pharmacogenetics" was first published in the late 1950s by Friedrich Vogel, the field has evolved into genome-wide association studies identifying novel variants associated with drug response phenotypes, international societies and consortia dedicated to pharmacogenomic research and clinical implementation, clinical practice guidelines, and the increasing availability of pharmacogenomic tests for healthcare providers in both hospital and primary care [...].
Topics: Genome-Wide Association Study; Humans; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 33801919
DOI: 10.3390/genes12030393 -
Human Mutation May 2011In the area of pharmacogenetics and personalized health care it is obvious that databases, providing important information of the occurrence and consequences of variant... (Review)
Review
In the area of pharmacogenetics and personalized health care it is obvious that databases, providing important information of the occurrence and consequences of variant genes encoding drug metabolizing enzymes, drug transporters, drug targets, and other proteins of importance for drug response or toxicity, are of critical value for scientists, physicians, and industry. The primary outcome of the pharmacogenomic field is the identification of biomarkers that can predict drug toxicity and drug response, thereby individualizing and improving drug treatment of patients. The drug in question and the polymorphic gene exerting the impact are the main issues to be searched for in the databases. Here, we review the databases that provide useful information in this respect, of benefit for the development of the pharmacogenomic field.
Topics: Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Polymorphism, Genetic; Precision Medicine
PubMed: 21309040
DOI: 10.1002/humu.21454 -
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 -
Trends in Pharmacological Sciences Aug 2011Pharmacogenomics in oncology holds the promise to personalize cancer therapy. However, its clinical application is still limited to a few genes, and, in the large... (Review)
Review
Pharmacogenomics in oncology holds the promise to personalize cancer therapy. However, its clinical application is still limited to a few genes, and, in the large majority of cancers, the correlation between genotype and clinical outcome has been disappointing. One possible explanation is that current pharmacogenomic studies do not take into account the emerging role of cancer stem cells (CSCs) in drug sensitivity and resistance. CSCs are a subpopulation of cells driven by specific signal-transduction pathways, but genetic variants affecting their activity are generally neglected in current pharmacogenomic studies. Moreover, in several malignancies, CSCs represent a rare sub-population; therefore, whole tumor profiling might mask CSC gene expression patterns. This article reviews current evidence on CSC chemoresistance and shows how common genetic variations in CSC-related genes may predict individual response to anti-cancer agents. Furthermore, we provide insights into the design of pharmacogenomic studies to address the clinical usefulness of CSC genetic profiling.
Topics: Animals; Antineoplastic Agents; Biomarkers; Cell Differentiation; Clinical Trials as Topic; Drug Resistance, Neoplasm; Humans; Mice; Models, Biological; Neoplasms; Neoplastic Stem Cells; Pharmacogenetics; Signal Transduction; Treatment Outcome
PubMed: 21529973
DOI: 10.1016/j.tips.2011.03.010 -
Pharmacogenomics Nov 2023With the aim of integrating clinical pharmacology with pharmacogenomics and providing a platform to gather clinicians, academicians, diagnostic laboratory personnel...
With the aim of integrating clinical pharmacology with pharmacogenomics and providing a platform to gather clinicians, academicians, diagnostic laboratory personnel and scientists from related domains, the International Conference on Clinical Pharmacology and Pharmacogenomics 2023 (ICCPP 2023) was jointly organized by the Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, India and the CANSEARCH research platform in Pediatric Oncology and Hematology, University of Geneva, Geneva, Switzerland. The conference was held on 31 August and 1 September 2023, as a continued Indo-Swiss scientific exchange event series. In this report we describe the proceedings of this conference for the benefit of peers who could not attend the conference but are interested in knowing about the scientific program in detail.
Topics: Child; Humans; Pharmacogenetics; Precision Medicine; Pharmacology, Clinical; Physicians; Switzerland
PubMed: 38009368
DOI: 10.2217/pgs-2023-0188 -
Drug Metabolism and Personalized Therapy Dec 2017
Topics: Humans; Pharmacogenetics; Precision Medicine; Societies, Scientific; Switzerland
PubMed: 29267167
DOI: 10.1515/dmpt-2017-0033