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Frontiers in Pharmacology 2023
PubMed: 37614312
DOI: 10.3389/fphar.2023.1267344 -
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 -
Differential drug response in pulmonary arterial hypertension: The potential for precision medicine.Pulmonary Circulation Oct 2023Pulmonary arterial hypertension (PAH) is a rare, complex, and deadly cardiopulmonary disease. It is characterized by changes in endothelial cell function and smooth... (Review)
Review
Pulmonary arterial hypertension (PAH) is a rare, complex, and deadly cardiopulmonary disease. It is characterized by changes in endothelial cell function and smooth muscle cell proliferation in the pulmonary arteries, causing persistent vasoconstriction, resulting in right heart hypertrophy and failure. There are multiple drug classes specific to PAH treatment, but variation between patients may impact treatment response. A small subset of patients is responsive to pulmonary vasodilators and can be treated with calcium channel blockers, which would be deleterious if prescribed to a typical PAH patient. Little is known about the underlying cause of this important difference in vasoresponsive PAH patients. Sex, race/ethnicity, and pharmacogenomics may also factor into efficacy and safety of PAH-specific drugs. Research has indicated that endothelin receptor antagonists may be more effective in women and there have been some minor differences found in certain races and ethnicities, but these findings are muddled by the impact of socioeconomic factors and a lack of representation of non-White patients in clinical trials. Genetic variants in genes such as , , , , , , and may influence the efficacy and safety of certain PAH-specific drugs. PAH research faces many challenges, but there is potential for new methodologies to glean new insights into PAH development and treatment.
PubMed: 37927610
DOI: 10.1002/pul2.12304 -
La Clinica Terapeutica 2023Colon cancer presents a complex pathophysiological landscape, which poses a significant challenge to the precise prediction of patient prognosis and treatment response.... (Review)
Review
Colon cancer presents a complex pathophysiological landscape, which poses a significant challenge to the precise prediction of patient prognosis and treatment response. However, the emergence of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has provided powerful tools to identify molecular alterations and pathways involved in colon cancer development and progression. To address the lack of literature exploring the intersection of omics sciences, precision medicine, and colon cancer, we conducted a comprehensive search in ScienceDirect and PubMed databases. We included systematic reviews, reviews, case studies, clinical studies, and randomized controlled trials that were published between 2015-2023. To refine our search, we excluded abstracts and non-English studies. This review provides a comprehensive summary of the current understanding of the latest developments in precision medicine and omics sciences in the context of colon cancer. Studies have identified molecular subtypes of colon cancer based on genomic and transcrip-tomic profiles, which have implications for prognosis and treatment selection. Furthermore, precision medicine (which involves tailoring treatments, based on the unique molecular characteristics of each patient's tumor) has shown promise in improving outcomes for colon cancer patients. Omics sciences and precision medicine hold great promise for identifying new therapeutic targets and developing more effective treatments for colon cancer. Although not strictly designed as a systematic review, this review provides a readily accessible and up-to-date summary of the latest developments in the field, highlighting the challenges and opportunities for future research.
Topics: Humans; Colonic Neoplasms; Genomics; Precision Medicine; Prognosis; Proteomics
PubMed: 37994749
DOI: 10.7417/CT.2023.2472 -
International Journal of Molecular... Dec 2023G protein-coupled receptors (GPCRs) and their downstream signaling pathways are critical targets for current pharmacotherapy [...].
G protein-coupled receptors (GPCRs) and their downstream signaling pathways are critical targets for current pharmacotherapy [...].
PubMed: 38203462
DOI: 10.3390/ijms25010291 -
Pharmacy (Basel, Switzerland) Dec 2023Pharmacogenomics (PGx) and the study of precision medicine has substantial power to either uplift health equity efforts or further widen the gap of our already existing... (Review)
Review
Pharmacogenomics (PGx) and the study of precision medicine has substantial power to either uplift health equity efforts or further widen the gap of our already existing health disparities. In either occurrence, the medication experience plays an integral role within this intersection on an individual and population level. Examples of this intertwined web are highlighted through a case discussion. With these perspectives in mind, several recommendations for the research and clinical communities are highlighted to promote equitable healthcare with PGx integrated.
PubMed: 38133461
DOI: 10.3390/pharmacy11060186 -
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 -
Pharmaceuticals (Basel, Switzerland) Mar 2024Antibiotic-related adverse events are common in both adults and children, and knowledge of the factors that favor the development of antibiotic-related adverse events is... (Review)
Review
Antibiotic-related adverse events are common in both adults and children, and knowledge of the factors that favor the development of antibiotic-related adverse events is essential to limit their occurrence and severity. Genetics can condition the development of antibiotic-related adverse events, and the screening of patients with supposed or demonstrated specific genetic mutations may reduce drug-related adverse events. This narrative review discusses which genetic variations may influence the risk of antibiotic-related adverse events and which conclusions can be applied to clinical practice. An analysis of the literature showed that defined associations between genetic variations and specific adverse events are very few and that, at the moment, none of them have led to the implementation of a systematic screening process for patients that must be treated with a given antibiotic in order to select those at risk of specific adverse events. On the other hand, in most of the cases, more than one variation is implicated in the determination of adverse events, and this can be a limitation in planning a systematic screening. Moreover, presently, the methods used to establish whether a patient carries a "dangerous" genetic mutation require too much time and waiting for the result of the test can be deleterious for those patients urgently requiring therapy. Further studies are needed to definitively confirm which genetic variations are responsible for an increased risk of a well-defined adverse event.
PubMed: 38543117
DOI: 10.3390/ph17030331 -
Pharmacogenomics and Personalized... 2023Pulmonary arterial hypertension (PAH) is a rare disease with heterogeneous causes that can lead to right ventricular (RV) failure and death if left untreated. There are... (Review)
Review
Pulmonary arterial hypertension (PAH) is a rare disease with heterogeneous causes that can lead to right ventricular (RV) failure and death if left untreated. There are currently 10 medications representative of five unique pharmacologic classes that are approved for treatment. These have led to significant improvements in overall clinical outcome. However, substantial variability in dosing requirements and treatment response is evident, leading to suboptimal outcome for many patients. Furthermore, dosing is empiric and iterative and can lead to delays in meeting treatment goals and burdensome adverse effects. Pharmacogenomic (PGx) associations have been reported with certain PAH medications, such as treprostinil and bosentan, and can explain some of the variability in response. Relevant genes associated with treprostinil include , and and are the genes encoding the major metabolizing liver enzymes for treprostinil, and reduced function variants (*2, *3) with were associated with lower treatment persistence. Additionally, a higher activity score was associated with a significantly less risk of treatment discontinuation. Other genes of interest that have been explored with treprostinil include , which is associated with right ventricular dysfunction and significantly higher dose requirements. Similarly, is associated with lower concentrations of cyclic adenosine monophosphate and significantly higher dose requirements. Genes of interest with the endothelin receptor antagonist (ERA) class include and . A genetic variant in (rs11157866) was linked to a significantly increased rate of clinical improvement with ERAs. The *2 variant with (encoding for the major metabolizing enzyme for bosentan) was significantly associated with a higher risk for elevations in hepatic aminotransferases and liver injury. In summary, this article reviews the relevant pharmacogenes that have been associated to date with dosing and outcome among patients who received PAH medications.
PubMed: 37457231
DOI: 10.2147/PGPM.S361222