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Annual Review of Pharmacology and... Jan 2024Interindividual variability in genes encoding drug-metabolizing enzymes, transporters, receptors, and human leukocyte antigens has a major impact on a patient's response... (Review)
Review
Interindividual variability in genes encoding drug-metabolizing enzymes, transporters, receptors, and human leukocyte antigens has a major impact on a patient's response to drugs with regard to efficacy and safety. Enabled by both technological and conceptual advances, the field of pharmacogenomics is developing rapidly. Major progress in omics profiling methods has enabled novel genotypic and phenotypic characterization of patients and biobanks. These developments are paralleled by advances in machine learning, which have allowed us to parse the immense wealth of data and establish novel genetic markers and polygenic models for drug selection and dosing. Pharmacogenomics has recently become more widespread in clinical practice to personalize treatment and to develop new drugs tailored to specific patient populations. In this review, we provide an overview of the latest developments in the field and discuss the way forward, including how to address the missing heritability, develop novel polygenic models, and further improve the clinical implementation of pharmacogenomics.
Topics: Humans; Pharmacogenetics; Membrane Transport Proteins; Technology
PubMed: 37506333
DOI: 10.1146/annurev-pharmtox-051921-091209 -
The Journal of Applied Laboratory... Jan 2024
Topics: Humans; Pharmacogenetics; Genotype; Precision Medicine
PubMed: 38167767
DOI: 10.1093/jalm/jfad064 -
Clinical Pharmacology and Therapeutics Jul 2023Over 20% of US Food and Drug Administration (FDA)-approved drugs in the United States are metabolized by the hepatic enzyme cytochrome P450 2D6 (CYP2D6). The gene... (Review)
Review
Over 20% of US Food and Drug Administration (FDA)-approved drugs in the United States are metabolized by the hepatic enzyme cytochrome P450 2D6 (CYP2D6). The gene encoding CYP2D6 is highly polymorphic and genetic variation has been shown to impact drug response for many commonly dispensed drugs including opioids and antidepressants. Thus, it is important to understand an individual's CYP2D6 metabolizer status to optimize treatment outcomes for patients taking medications that are metabolized by this enzyme. Consequently, clinical CYP2D6 pharmacogenetic testing is being implemented by a growing number of health centers. Furthermore, clinical guidelines currently recommend adapting therapeutic regimens based on CYP2D6 genotype-informed phenotype. However, CYP2D6 genetic variation varies considerably across global populations and many allelic variants, or star alleles, are predominantly found in certain ancestral populations. Although CYP2D6 genetic variation has been extensively studied, there is still a paucity of information for many non-European populations. As has been shown for other pharmacogenes in randomized controlled trials, results from European populations cannot simply be extrapolated to other groups and, in some cases, even has the potential to cause harm. Therefore, enhanced inclusion in pharmacogenetic studies is urgently needed to increase ancestral representation, determine the extent of global CYP2D6 genetic variation (e.g., ancestry-specific variants), and determine the clinical impact of this variation on clinical treatment outcome. This review highlights knowledge gaps, challenges, and future directions in CYP2D6 pharmacogenomics through a unique pharmacoequity lens to address health inequities that hamper our ability to optimize drug therapy for improved pharmacological outcomes in diverse populations globally.
Topics: Cytochrome P-450 CYP2D6; Pharmacogenetics; Genotype; Antidepressive Agents; Pharmaceutical Preparations
PubMed: 36924260
DOI: 10.1002/cpt.2890 -
Pharmacogenomics Nov 2023Tweetable abstract Accurate variant interpretation has become a key bottleneck for the translation of an individual's pharmacogenome into actionable recommendations. We...
Tweetable abstract Accurate variant interpretation has become a key bottleneck for the translation of an individual's pharmacogenome into actionable recommendations. We recommend an integrated use of multiplexed assays, structure-based predictions and biobank data to develop more accurate effect predictors.
Topics: Humans; Pharmacogenomic Variants; Precision Medicine
PubMed: 37846582
DOI: 10.2217/pgs-2023-0187 -
Medicina Clinica Feb 2024
Topics: Humans; Pharmacogenetics; Precision Medicine
PubMed: 38142210
DOI: 10.1016/j.medcli.2023.11.008 -
Biochimica Et Biophysica Acta.... Feb 2024Thyroid cancer is one of the most common tumors of the endocrine system because of its rapid and steady increase in incidence and prevalence. In recent years, a growing... (Review)
Review
Thyroid cancer is one of the most common tumors of the endocrine system because of its rapid and steady increase in incidence and prevalence. In recent years, a growing number of studies have identified a key role for the gut, thyroid tissue and oral microbiota in the regulation of metabolism and the immune system. A growing body of evidence has conclusively demonstrated that the microbiota influences tumor formation, prevention, diagnosis, and treatment. We provide extensive information in which oral, gut, and thyroid microbiota have an effect on thyroid cancer development in this review. In addition, we thoroughly discuss the various microbiota species, their potential functions, and the underlying mechanisms for thyroid cancer. The microbiome offers a unique opportunity to improve the effectiveness of immunotherapy and radioiodine therapy thyroid cancer by maintaining the right type of microbiota, and holds great promise for improving clinical outcomes and quality of life for thyroid cancer patients.
Topics: Humans; Iodine Radioisotopes; Quality of Life; Thyroid Neoplasms; Microbiota
PubMed: 38029942
DOI: 10.1016/j.bbadis.2023.166971 -
Pharmacogenomics Nov 2023To advance clinical adoption and implementation of pharmacogenomics (PGx) testing, barriers and facilitators to these efforts must be understood. This study identified...
To advance clinical adoption and implementation of pharmacogenomics (PGx) testing, barriers and facilitators to these efforts must be understood. This study identified and examined barriers and facilitators to active implementation of a PGx program across multiple clinic settings in an academic healthcare system. 28 contributors to the PGx implementation (e.g., clinical providers, informatics specialists) completed an interview to elicit their perceptions of the implementation. Qualitative analysis identified several barriers and facilitators that spanned different stages of the implementation process. Specifically, unclear test payment mechanisms, decision support tool development, rigid workflows and provider education were noted as barriers to the PGx implementation. A multidisciplinary implementation team and leadership support emerged as key facilitators. Furthermore, participants also suggested strategies to overcome or maintain these factors. Assessing real-world implementation perceptions and suggested strategies from a range of implementation contributors facilitates a more comprehensive framework and best-practice guidelines for PGx implementation.
Topics: Humans; Pharmacogenetics; Delivery of Health Care
PubMed: 37975236
DOI: 10.2217/pgs-2023-0179 -
American Journal of Pharmaceutical... Sep 2023Incorporating diversity, equity, inclusion, and anti-racism principles into clinical and didactic education is essential because each influence cognitive and affective... (Review)
Review
OBJECTIVE
Incorporating diversity, equity, inclusion, and anti-racism principles into clinical and didactic education is essential because each influence cognitive and affective attitudes in pharmacy practice. Educators must learn from the past to enlighten the future. For example, race is a social construct, not a biological construct. However, it persistently acts as a surrogate for determining medical diagnoses and treatment.
FINDINGS
Precision medicine and pharmacogenomics can serve as a basis for deconstructing social constructs surrounding race and other social determinants of health.
SUMMARY
In this review, the authors highlight why using race in health education will lead to less-than-optimal clinical decisions and discuss best practices for incorporating diversity, equity, inclusion, and anti-racism into health education from a pharmacogenomic-based perspective.
Topics: Humans; Education, Pharmacy; Pharmacy; Antiracism; Educational Status; Health Education
PubMed: 37714655
DOI: 10.1016/j.ajpe.2023.100077 -
Pharmacogenomics Aug 2023Precision medicine has revolutionized clinical care for patients with cancer through the development of targeted therapy, identification of inherited cancer... (Review)
Review
Precision medicine has revolutionized clinical care for patients with cancer through the development of targeted therapy, identification of inherited cancer predisposition syndromes and the use of pharmacogenetics to optimize pharmacotherapy for anticancer drugs and supportive care medications. While germline (patient) and somatic (tumor) genomic testing have evolved separately, recent interest in paired germline/somatic testing has led to an increase in integrated genomic testing workflows. However, paired germline/somatic testing has generally lacked the incorporation of germline pharmacogenomics. Integrating pharmacogenomics into paired germline/somatic genomic testing would be an efficient method for increasing access to pharmacogenomic testing. In this perspective, the authors argue for the benefits of implementing a comprehensive approach integrating somatic and germline testing that is inclusive of pharmacogenomics in clinical practice.
PubMed: 37702060
DOI: 10.2217/pgs-2023-0125 -
Annual Review of Pharmacology and... Jan 2024The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic... (Review)
Review
The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied, selection of study participants, and methods used to collect and analyze data. To examine the representation of biogeographical populations in pharmacogenomic data sets, we describe individuals involved in gene-drug response studies from PharmGKB, a leading repository of drug-gene annotations, and showcase, a gene that metabolizes approximately 25% of all prescribed drugs. We also show how the historical underrepresentation of females in clinical trials has led to significantly more adverse drug reactions in females than in males.
Topics: Male; Humans; Female; Sexism; Pharmacogenetics; Drug-Related Side Effects and Adverse Reactions
PubMed: 37450899
DOI: 10.1146/annurev-pharmtox-030823-111731