-
Pharmacy (Basel, Switzerland) Sep 2023Since the rebirth of pharmacogenomics (PGx) in the 1990s and 2000s, with new discoveries of genetic variation underlying adverse drug response and new analytical... (Review)
Review
Since the rebirth of pharmacogenomics (PGx) in the 1990s and 2000s, with new discoveries of genetic variation underlying adverse drug response and new analytical technologies such as sequencing and microarrays, there has been much interest in the clinical application of PGx testing. The early involvement of pharmacists in clinical studies and the establishment of organizations to support the dissemination of information about PGx variants have naturally resulted in leaders in clinical implementation. This paper presents an overview of the evolving role of pharmacists, and discusses potential challenges and future paths, primarily focused in the U.S. Pharmacists have positioned themselves as leaders in clinical PGx testing, and will prepare the next generation to utilize PGx testing in their scope of practice.
PubMed: 37736916
DOI: 10.3390/pharmacy11050144 -
Clinical and Translational Science Dec 2023Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals'... (Review)
Review
Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals' (HCPs) and consumers' knowledge, attitudes, perspectives, and education needs to inform strategies for implementation of scalable and sustainable oncology PGx programs. Systematic review of original articles indexed in EMBASE, EMCARE, MEDLINE, and PsycInfo from January 2012 until June 2022, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using the Mixed Methods Appraisal Tool. PROSPERO registration number CRD42022352348. Of 1442 identified studies; 23 met inclusion criteria with 87% assessed high quality. Of these, 52% reported on HCPs, 35% on consumers, and 13% on both HCPs and consumers. Most were conducted in the United States (70%) and included multiple cancer types (74%). Across studies, HCPs and consumers mostly perceived value in PGx, however, both groups reported barriers to utilization, including cost, lack of consistent recommendations across guidelines, and limited knowledge among HCPs; test accuracy, clear testing benefits, and genomic information confidentiality among consumers. HCPs and consumers value and want to engage in PGx strategies in oncology care, however, are inhibited by unmet needs and practice and knowledge gaps. Implementation strategies aimed at addressing these issues may best support increased PGx uptake in oncology practice.
Topics: Humans; Pharmacogenetics; Health Knowledge, Attitudes, Practice; Health Personnel; Medical Oncology; Neoplasms
PubMed: 37991131
DOI: 10.1111/cts.13672 -
Pharmacological Research Feb 2024The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support,...
The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support, many research groups, composed of basic and clinical researchers, have been actively working for decades in this field. Their contributions made an international impact and paved the way for further studies and pharmacogenomics implementation in clinical practice. In this manuscript, that makes part of the Special Issue entitled Spanish Pharmacology, we present an analysis of the state of the art of Pharmacogenetics and Pharmacogenomics research in Europe, we compare it with the developments in Spain, and we summarize the most salient contributions since 1988 to the present, as well as recent developments in the clinical application of pharmacogenomics knowledge. Finally, we present some considerations on how we could improve translation to clinical practice in this specific scenario.
Topics: Pharmacogenetics; Precision Medicine; Europe
PubMed: 38199278
DOI: 10.1016/j.phrs.2024.107061 -
Journal of Clinical PsychopharmacologyThe purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression.
METHODS
Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model.
RESULTS
Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters.
CONCLUSION
Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.
Topics: Humans; Antidepressive Agents; Bipolar Disorder; Mania; Pharmacogenetics; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 37683232
DOI: 10.1097/JCP.0000000000001747 -
Genes Nov 2023Advances in pharmacogenomics have paved the way for personalized medicine. Cardiovascular diseases still represent the leading cause of mortality in the world. The aim... (Review)
Review
PURPOSE OF REVIEW
Advances in pharmacogenomics have paved the way for personalized medicine. Cardiovascular diseases still represent the leading cause of mortality in the world. The aim of this review is to summarize the background, rationale, and evidence of pharmacogenomics in cardiovascular medicine, in particular, the use of antiplatelet drugs, anticoagulants, and drugs used for the treatment of dyslipidemia.
RECENT FINDINGS
Randomized clinical trials have supported the role of a genotype-guided approach for antiplatelet therapy in patients with coronary heart disease undergoing percutaneous coronary interventions. Numerous studies demonstrate how the risk of ineffectiveness of new oral anticoagulants and vitamin K anticoagulants is linked to various genetic polymorphisms. Furthermore, there is growing evidence to support the association of some genetic variants and poor adherence to statin therapy, for example, due to the appearance of muscular symptoms. There is evidence for resistance to some drugs for the treatment of dyslipidemia, such as anti-PCSK9.
SUMMARY
Pharmacogenomics has the potential to improve patient care by providing the right drug to the right patient and could guide the identification of new drug therapies for cardiovascular disease. This is very important in cardiovascular diseases, which have high morbidity and mortality. The improvement in therapy could be reflected in the reduction of healthcare costs and patient mortality.
Topics: Humans; Pharmacogenetics; Cardiovascular Agents; Cardiovascular Diseases; Anticoagulants; Dyslipidemias
PubMed: 38003001
DOI: 10.3390/genes14112057 -
BioRxiv : the Preprint Server For... Aug 2023Spatial cellular heterogeneity contributes to differential drug responses in a tumor lesion and potential therapeutic resistance. Recent emerging spatial technologies...
UNLABELLED
Spatial cellular heterogeneity contributes to differential drug responses in a tumor lesion and potential therapeutic resistance. Recent emerging spatial technologies such as CosMx SMI, MERSCOPE, and Xenium delineate the spatial gene expression patterns at the single cell resolution. This provides unprecedented opportunities to identify spatially localized cellular resistance and to optimize the treatment for individual patients. In this work, we present a graph-based domain adaptation model, SpaRx, to reveal the heterogeneity of spatial cellular response to drugs. SpaRx transfers the knowledge from pharmacogenomics profiles to single-cell spatial transcriptomics data, through hybrid learning with dynamic adversarial adaption. Comprehensive benchmarking demonstrates the superior and robust performance of SpaRx at different dropout rates, noise levels, and transcriptomics coverage. Further application of SpaRx to the state-of-art single-cell spatial transcriptomics data reveals that tumor cells in different locations of a tumor lesion present heterogenous sensitivity or resistance to drugs. Moreover, resistant tumor cells interact with themselves or the surrounding constituents to form an ecosystem for drug resistance. Collectively, SpaRx characterizes the spatial therapeutic variability, unveils the molecular mechanisms underpinning drug resistance, and identifies personalized drug targets and effective drug combinations.
KEY POINTS
We have developed a novel graph-based domain adaption model named SpaRx, to reveal the heterogeneity of spatial cellular response to different types of drugs, which bridges the gap between pharmacogenomics knowledgebase and single-cell spatial transcriptomics data.SpaRx is developed tailored for single-cell spatial transcriptomics data and is provided available as a ready-to-use open-source software, which demonstrates high accuracy and robust performance.SpaRx uncovers that tumor cells located in different areas within tumor lesion exhibit varying levels of sensitivity or resistance to drugs. Moreover, SpaRx reveals that tumor cells interact with themselves and the surrounding microenvironment to form an ecosystem capable of drug resistance.
PubMed: 37577665
DOI: 10.1101/2023.08.03.551911 -
Journal of Pharmaceutical Policy and... 2024Pharmacogenomics, a key component of precision medicine, aims to improve healthcare outcomes. As pharmacists play a pivotal role in this evolving field, an assessment of...
BACKGROUND
Pharmacogenomics, a key component of precision medicine, aims to improve healthcare outcomes. As pharmacists play a pivotal role in this evolving field, an assessment of their preparedness to apply pharmacogenomics is imperative.
METHODS
In this cross-sectional study, a validated questionnaire (Content Validity Ratio > 0.741, < 0.05) that demonstrated reliability (Cronbach's alpha for all scales > 0.7) gathered data on demographics, knowledge, attitudes, barriers, and confidence in pharmacogenomics among pharmacists and pharmacy students in Jordan. Statistical analysis assessed associations and their strength within the collected data and variables.
RESULTS
This study included 514 pharmacists and pharmacy students. Knowledge scores were moderate and correlated with academic level and pharmacy school attended. Most participants were open to providing pharmacogenomics testing and interpretation through pharmacy services, but the majority demonstrated concerns about potential misinterpretation of test results and the resulting patients' anxiety. Students cited limited accessibility, while pharmacists identified the lack of standardised guidelines as the main roadblock.
CONCLUSION
This study highlights the need for education to prepare pharmacists for their role in pharmacogenomics. Despite positive attitudes from pharmacists, addressing knowledge gaps, the low confidence in recommending pharmacogenomics tests, and concerns about implementation are essential.
PubMed: 38868176
DOI: 10.1080/20523211.2024.2354879 -
International Journal of Molecular... Apr 2024In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia... (Review)
Review
In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the appropriate drug and the correct dosage for each patient. We first discussed the search for DNA polymorphisms associated with a high expression of γ-globin genes and identified this using GWAS studies and CRISPR-based gene editing approaches. We then presented validated DNA polymorphisms associated with a high HbF production (including, but not limited to the XmnI polymorphism and those related to the , , , and genes). The expression of microRNAs involved in the regulation of γ-globin genes was also presented in the context of pharmacomiRNomics. Then, the pharmacogenomics of validated fetal hemoglobin inducers (hydroxyurea, butyrate and butyrate analogues, thalidomide, and sirolimus), of iron chelators, and of analgesics in the pain management of SCD patients were considered. Finally, we discuss current clinical trials, as well as international research networks focusing on clinical issues related to pharmacogenomics in hematological diseases.
Topics: Humans; Anemia, Sickle Cell; beta-Thalassemia; Pharmacogenetics; Fetal Hemoglobin; gamma-Globins; Iron Chelating Agents
PubMed: 38673849
DOI: 10.3390/ijms25084263 -
Biomedicines May 2024The safety of the use of psychotropic drugs, widely used in neurological and psychiatric practice, is an urgent problem in personalized medicine. This narrative review... (Review)
Review
The safety of the use of psychotropic drugs, widely used in neurological and psychiatric practice, is an urgent problem in personalized medicine. This narrative review demonstrated the variability in allelic frequencies of low-functioning and non-functional single nucleotide variants in genes encoding key isoenzymes of valproic acid P-oxidation in the liver across different ethnic/racial groups. The sensitivity and specificity of pharmacogenetic testing panels for predicting the rate of metabolism of valproic acid by P-oxidation can be increased by prioritizing the inclusion of the most common risk allele characteristic of a particular population (country).
PubMed: 38790997
DOI: 10.3390/biomedicines12051036 -
The Veterinary Clinics of North... Nov 2023Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause... (Review)
Review
Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause cardiomyopathies in humans with only a handful known in cats and dogs. This review highlights the need and use of personalized one-health approaches to cardiovascular case management and advancement in pharmacogenetic-based therapy in veterinary medicine. Personalized medicine holds promise in understanding the molecular basis of disease and ultimately will unlock the next generation of targeted novel pharmaceuticals and aid in the reversal of detrimental effects at a molecular level.
Topics: Humans; Animals; Cats; Dogs; Pets; Precision Medicine; Veterinary Drugs; Cardiomyopathies; Cardiology; Cat Diseases; Dog Diseases
PubMed: 37423841
DOI: 10.1016/j.cvsm.2023.05.016