☆ 4.6 Review

Pharmacogenomics: Driving Personalized Medicine

PHARMACOLOGICAL REVIEWS (2023)

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Article Immunology

Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients

Ronza Najjar-Debbiny et al.

Summary: This study assessed the effectiveness of Paxlovid in high-risk COVID-19 patients in real-world settings. The findings demonstrate that Paxlovid is highly effective in reducing the risk of death and severe COVID-19 in the Omicron era. The study also suggests that Paxlovid may be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease. Vaccination status did not significantly impact the effectiveness of Paxlovid.

CLINICAL INFECTIOUS DISEASES (2023)

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Article Biochemistry & Molecular Biology

Database resources of the National Center for Biotechnology Information in 2023

Eric W. Sayers et al.

Summary: The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank nucleic acid sequence database and the PubMed database of citations and abstracts published in life science journals. NCBI offers search and retrieval operations through 35 distinct databases, most of which are accessed through the E-utilities programming interface. Recent additions to the resources include the Comparative Genome Resource (CGR) and the BLAST ClusteredNR database. Significant updates have been made to resources such as PubMed, PMC, Bookshelf, IgBLAST, GDV, and RefSeq in the past year.

NUCLEIC ACIDS RESEARCH (2023)

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Article Biotechnology & Applied Microbiology

Implementation of pharmacogenomics into inpatient general medicine

Thomas Chen et al.

Summary: Pharmacogenomics is an important part of personalized medicine that is not widely used in the inpatient setting. This study in Chicago aimed to implement pharmacogenomics into inpatient practice at three sites and reported on the barriers encountered and solutions employed. Strategies included a streamlined delivery system, engagement with hospitalists and general medical providers, and optimizing system function. The work provides insights into strategies for implementing pharmacogenomics in the inpatient setting.

PHARMACOGENETICS AND GENOMICS (2023)

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Article Pharmacology & Pharmacy

A comprehensive pharmacogenomic study indicates roles for SLCO1B1, ABCG2 and SLCO2B1 in rosuvastatin pharmacokinetics

Minna Lehtisalo et al.

Summary: This study comprehensively investigated the effects of genetic variability on the pharmacokinetics of rosuvastatin. The findings suggest that SLCO1B1, ABCG2, and SLCO2B1 genes play roles in rosuvastatin pharmacokinetics. Poor SLCO1B1 or ABCG2 function genotypes may increase the risk of rosuvastatin-induced myotoxicity.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2023)

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Article Oncology

The impact of endoxifen-guided tamoxifen dose reductions on endocrine side-effects in patients with primary breast cancer

S. M. Buijs et al.

Summary: This study found that dose reduction of tamoxifen based on endoxifen levels can decrease its side-effects and improve patients' quality of life.

ESMO OPEN (2023)

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Article Hematology

A MIR17HG-derived long noncoding RNA provides an essential chromatin scaffold for protein interaction and myeloma growth

Eugenio Morelli et al.

Summary: In this study, the lncRNA lnc-17-92 derived from MIR17HG was found to play a crucial role in cell growth dependency in multiple myeloma. It acts independently of microRNA and DROSHA and functions by providing a chromatin scaffold for the interaction between c-MYC and WDR82, leading to the expression of the important gene ACACA. Targeting MIR17HG pre-RNA with clinically applicable antisense molecules disrupts the activities of lnc-17-92 and shows potent antitumor effects in preclinical models.

BLOOD (2023)

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Article Pharmacology & Pharmacy

CYP2D6 and CYP2C8 pharmacogenetics and pharmacological interactions to predict imatinib plasmatic exposure in GIST patients

Chiara Dalle Fratte et al.

Summary: This study investigated the association between gene activity score and imatinib exposure in GIST patients. The results showed that CYP2D6 plays a major role in imatinib pharmacokinetics, but other factors such as CYP2C8 may also influence the drug's exposure. These findings could help identify patients who are more susceptible to imatinib under- or overexposure for personalized treatment and monitoring strategies.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2023)

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Article Pharmacology & Pharmacy

Cross-Ancestry Genome-Wide Association Study Defines the Extended CYP2D6 Locus as the Principal Genetic Determinant of Endoxifen Plasma Concentrations

Chiea Chuen Khor et al.

Summary: The extended CYP2D6 locus at 22q13 is the principal genetic determinant of endoxifen plasma concentration, as revealed by the first cross-ancestry genome-wide association study. Functional analysis showed that 66% of the associated variants in this region were significantly correlated with hepatic CYP2D6 activity or expression. Machine learning models demonstrated that hotspot variants in this region, combined with CYP2D6 activity score, could explain a significant portion of the variability in tamoxifen metabolites.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2023)

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Article Pharmacology & Pharmacy

How to Run the Pharmacogenomics Clinical Annotation Tool (PharmCAT)

Binglan Li et al.

Summary: Pharmacogenomics (PGx) investigates the genetic influence on drug response and is important for precision medicine. The challenge lies in interpreting PGx testing results for clinical decision support. PharmCAT has been designed to provide automatic interpretations of patient genetic data and generate reports with guideline recommendations. It has introduced new features, such as a VCF Preprocessor and functionalities for PGx research.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2023)

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Article Pharmacology & Pharmacy

Pharmacokinetic Drug-Drug Interactions with Drugs Approved by the US Food and Drug Administration in 2020: Mechanistic Understanding and Clinical RecommendationsS

Jingjing Yu et al.

Summary: This study analyzed drug-drug interaction (DDI) data for small molecular drugs approved by the US Food and Drug Administration in 2020. The results showed that oncology drugs were the most represented therapeutic area, and inhibition and induction of CYP3A played a significant role in clinical interactions. Several sensitive substrates and strong inhibitors were identified.

DRUG METABOLISM AND DISPOSITION (2022)

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Review Pharmacology & Pharmacy

Racial and Ethnic Differences in Drug Disposition and Response: Review of New Molecular Entities Approved Between 2014 and 2019

Anuradha Ramamoorthy et al.

Summary: This study reported that about 10% of new molecular entities approved by the US Food and Drug Administration between 2014 and 2019 showed differences in exposure and/or response based on race/ethnicity or pharmacogenetic factors. The findings indicated a decrease in differences in labeling when compared to the period between 2008 and 2013, where approximately 21% of new molecular entities had differences in pharmacokinetics, safety, response, and/or pharmacogenetics.

JOURNAL OF CLINICAL PHARMACOLOGY (2022)

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Review Biochemistry & Molecular Biology

Revisiting sORFs: overcoming challenges to identify and characterize functional microproteins

Dorte Schlesinger et al.

Summary: Short ORFs (sORFs), which contain a start and stop codon within 100 codons, can be found in organisms across all domains of life and often outnumber annotated protein-coding ORFs. Recent advancements in technology have led to the identification of thousands of potential coding sORFs, shedding light on the overlooked coding potential of these small proteins. The emerging field of microproteins in eukaryotes shows promise for uncovering new functional small proteins encoded in the genome.

FEBS JOURNAL (2022)

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Letter Medicine, General & Internal

Ultrarapid Nanopore Genome Sequencing in a Critical Care Setting

John E. Gorzynski et al.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Pharmacology & Pharmacy

Prioritizing pharmacogenomics implementation initiates - survey of healthcare professionals

Teresa T. Ho et al.

Summary: Survey results showed that most clinicians believed pharmacogenomics would be useful in their clinical practice, but they do not feel prepared to interpret pharmacogenomic results.

PERSONALIZED MEDICINE (2022)

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Article Multidisciplinary Sciences

Interpreting coronary artery disease GWAS results: A functional genomics approach assessing biological significance

Katherine Hartmann et al.

Summary: This study used RNA sequencing data and allelic expression imbalance data from GTEx to expand the list of candidate genes and variants in coronary artery disease (CAD) GWAS. The findings suggest that multiple functional variants exist within loci and non-coding RNAs may play a significant role in CAD. These results improve our understanding of the biological basis and gene regulation in CAD.

PLOS ONE (2022)

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Review Genetics & Heredity

Maturation and application of phenome-wide association studies

Shiying Liu et al.

Summary: Phenome-wide association studies (PheWAS) have significantly advanced in the past decade, uncovering novel genotype-phenotype relationships. With advancements in methods and resources, the potential of PheWAS has been realized to a greater extent, but challenges remain in further understanding the complex genetic architecture underlying human diseases and traits.

TRENDS IN GENETICS (2022)

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Review Oncology

Independent Drug Action in Combination Therapy: Implications for Precision Oncology

Deborah Plana et al.

Summary: Combination therapies are more effective in treating cancer than monotherapy, addressing tumor heterogeneity. The model of independent drug action provides multiple opportunities for benefit from at least one drug, and personalized, targeted combination therapy can increase therapeutic benefits.

CANCER DISCOVERY (2022)

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Article Oncology

Comprehensive Analysis of Somatic Reversion Mutations in Homologous Recombination Repair (HRR) Genes in A Large Cohort of Chinese Pan-cancer Patients

Hong Zong et al.

Summary: This study comprehensively characterizes the prevalence and characteristics of reversion mutations in homologous recombination repair (HRR)-related genes in a large cohort of Chinese pan-cancer patients. The study reveals that reversion mutations predominantly occur in BRCA1, BRCA2, and PALB2, and often develop after resistance to platinum-based chemotherapy and/or PARP inhibitors.

JOURNAL OF CANCER (2022)

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Review Pharmacology & Pharmacy

HLA Allele-Restricted Immune-Mediated Adverse Drug Reactions: Framework for Genetic Prediction

Kanoot Jaruthamsophon et al.

Summary: This review explores the translational progress of using HLA as a key susceptibility factor for immune ADRs and highlights gaps in our knowledge. Additionally, it covers relevant findings of HLA-mediated drug-specific T cell activation.

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY (2022)

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Article Pharmacology & Pharmacy

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype

John Henry McDermott et al.

Summary: The use of aminoglycosides is associated with the risk of hearing loss, particularly in individuals with MT-RNR1 gene variants. It is advisable to avoid using aminoglycosides in individuals with MT-RNR1 variants associated with an increased risk of aminoglycoside-induced hearing loss.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2022)

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Review Genetics & Heredity

Advancing Pharmacogenomics from Single-Gene to Preemptive Testing

Cyrine E. Haidar et al.

Summary: Pharmacogenomic testing is effective in enhancing medication safety and efficacy. However, preemptive testing poses logistical concerns, such as reimbursement, result reporting, and portability. Lessons can be learned from institutions that have implemented preemptive testing.

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS (2022)

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Editorial Material Genetics & Heredity

Pharmacogenomics: the low-hanging fruit in the personalized medicine tree

George P. Patrinos et al.

HUMAN GENETICS (2022)

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Article Biotechnology & Applied Microbiology

Regulation of CYP3A4 and CYP3A5 by a lncRNA: a potential underlying mechanism explaining the association between CYP3A4*1G and CYP3A metabolism

Joseph M. Collins et al.

Summary: In this study, a novel lncRNA called AC069294.1 was found to regulate the expression of CYP3A4 and CYP3A5. The mutation CYP3A4*1G was associated with increased expression of AC069294.1 and decreased expression of both CYP3A4 and CYP3A5. These findings suggest that the expression of AC069294.1 may contribute to inter-person variability in CYP3A4 and CYP3A5.

PHARMACOGENETICS AND GENOMICS (2022)

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Article Oncology

Association of CD274 (PD-L1) Copy Number Changes with Immune Checkpoint Inhibitor Clinical Benefit in Non-Squamous Non-Small Cell Lung Cancer

Karthikeyan Murugesan et al.

Summary: This study investigated the response to immune checkpoint inhibitors in non-squamous non-small cell lung cancer patients. The results showed that CD274 copy number gains at different thresholds can predict different responses to ICI treatment. Further clinical trials are needed to validate these findings.

ONCOLOGIST (2022)

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Article Multidisciplinary Sciences

Idiosyncratic epistasis leads to global fitness-correlated trends

Christopher W. Bakerlee et al.

Summary: Epistasis plays a significant role in evolutionary trajectories, with idiosyncratic interactions observed among specific mutations. Protein-level fitness landscapes have shown such interactions, while genome-wide mutations demonstrate ubiquitous patterns of diminishing-returns and increasing-costs epistasis.

SCIENCE (2022)

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Article Multidisciplinary Sciences

An immune gene signature to predict prognosis and immunotherapeutic response in lung adenocarcinoma

Hongquan Chen et al.

Summary: This study constructed a stable immune gene signature for lung adenocarcinoma patients, which can be used to predict prognosis and the benefits of immune checkpoint inhibitors (ICIs) treatment. The research found that the low-risk group of the immune gene signature had a higher survival rate and lower gene mutation rate, which were associated with a better prognosis. In contrast, the high-risk group had higher immune cell infiltration but was associated with a poorer prognosis.

SCIENTIFIC REPORTS (2022)

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Review Cardiac & Cardiovascular Systems

Somatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular Risk

Bernhard Haring et al.

Summary: This review summarizes the role of clonal hematopoiesis of indeterminate potential (CHIP) as a cardiovascular risk factor. It has been found that CHIP is associated with accelerated atherosclerosis and cardiovascular disease. The most commonly mutated genes are DNMT3A, TET2, JAK2, and ASXL1, and the underlying mechanisms are predominantly related to inflammatory pathways. In addition to age, smoking, obesity/type 2 diabetes, and an unhealthy diet may also contribute to the occurrence of somatic mutations.

CURRENT CARDIOLOGY REPORTS (2022)

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Article

Different Arrangement of Dopamine Receptors/NMDA Receptors Heterocomplexes in the Brain Regions of a Healthy Male, Female and Audiogenic Seizure-Prone Male Rats

Gigi Tevzadze et al.

American Journal of Biochemistry and Biotechnology (2022)

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Article Genetics & Heredity

Genetic interactions drive heterogeneity in causal variant effect sizes for gene expression and complex traits

Roshni A. Patel et al.

Summary: This study developed a method to test the influence of gene-by-gene and gene-by-environment interactions on complex traits in humans. By testing SNPs in regions of European ancestry shared between European American and admixed African American individuals, the study found that genetic interactions modify the effect sizes of causal variants in human complex traits.

AMERICAN JOURNAL OF HUMAN GENETICS (2022)

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Article Oncology

Selective poly adenylation predicts the efficacy of immunotherapy in patients with lung adenocarcinoma by multiple omics research

Liusheng Wu et al.

Summary: This study aimed to investigate the application value of selective polyadenylation in lung adenocarcinoma (LUAD), particularly in immune cell infiltration, biological transcription function, and survival prognosis. The research analyzed mRNA expression data and immune cell content from LUAD patients to construct a LUAD risk score prognostic model. The study found that the immune score significantly affected the prognosis of LUAD patients, and identified specific immune cell types and immunosuppressor genes correlated with the risk score. The findings highlight the importance of selective polyadenylation in LUAD development, immune invasion, and survival prognosis.

ANTI-CANCER DRUGS (2022)

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Review Pharmacology & Pharmacy

Targeted therapy for breast cancer: An overview of drug classes and outcomes

Aaron T. Jacobs et al.

Summary: Over the past 25 years, there has been significant growth in new therapeutic options for breast cancer, known as targeted therapies that block specific pathways to inhibit tumor growth and survival. This review examines the development and impact of targeted therapies in clinical use, summarizing clinical data and adverse effects in different breast cancer subtypes.

BIOCHEMICAL PHARMACOLOGY (2022)

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Article Oncology

Discovery and validation of a transcriptional signature identifying homologous recombination-deficient breast, endometrial and ovarian cancers

Guillaume Beinse et al.

Summary: This study identified a common transcriptional profile shared by endometrial, breast, and ovarian cancers with homologous recombination deficiency (HRD). The RNAseq score derived from this profile was predictive of HRD and correlated with HRD in independent gynecological cancer datasets. The RNAseq HRD profile was associated with better overall survival in certain subtypes of these cancers and could potentially be used for prognostication and therapeutic decision-making.

BRITISH JOURNAL OF CANCER (2022)

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Editorial Material Multidisciplinary Sciences

Legal reform to enhance global text and data mining research

Sean M. Fiil-Flynn et al.

SCIENCE (2022)

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Review Oncology

Using Circulating Tumor DNA in Colorectal Cancer: Current and Evolving Practices

Midhun Malla et al.

Summary: Circulating tumor DNA (ctDNA) plays a crucial role in the personalized management of colorectal cancer, serving as a promising prognostic and predictive biomarker for detecting disease residual, early recurrence, and molecular profiling. Prospective studies focusing on minimal residual disease (MRD) are essential for further understanding the clinical applications of ctDNA.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Medicine, General & Internal

PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer

Andrea Cercek et al.

Summary: This study found that mismatch repair-deficient, locally advanced rectal cancer is highly sensitive to PD-1 blockade. Additionally, no adverse events of grade 3 or higher have been reported, and no cases of progression or recurrence have been observed. Longer follow-up is needed to assess the duration of response.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Review Pharmacology & Pharmacy

Genetics of drug-induced QT prolongation: evaluating the evidence for pharmacodynamic variants

Ana Lopez-Medina et al.

Summary: Drug-induced long QT syndrome (diLQTS) is a potential adverse effect of commonly prescribed drugs, increasing the risk of lethal ventricular arrhythmias. Genetic variants in pharmacodynamic genes have been associated with diLQTS. Evaluating the strength of evidence for these variants through a semiquantitative scoring system, it was found that KCNE1-D85N and KCNE2-T8A have definitive and strong evidence, supporting their consideration as risk factors for patients prescribed QT-prolonging drugs.

PHARMACOGENOMICS (2022)

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Article Pharmacology & Pharmacy

Development of pharmacogenomic algorithm to optimize nateglinide dose for the treatment of type 2 diabetes mellitus

Shaik Mohammad Naushad et al.

Summary: This study developed a pharmacogenomic algorithm to optimize nateglinide therapy. The results showed the association of CYP2C9, SLCO1B1, and MTNR1B genotypes with the safety and efficacy of nateglinide. This algorithm helps ensure the safety and efficacy of nateglinide therapy.

PHARMACOLOGICAL REPORTS (2022)

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Article Biochemistry & Molecular Biology

Transcription Factors and ncRNAs Associated with CYP3A Expression in Human Liver and Small Intestine Assessed with Weighted Gene Co-Expression Network Analysis

Huina Huang et al.

Summary: By analyzing gene co-expression networks, it was discovered that lncRNAs play a significant role in the regulation of CYP3A expression and are associated with transcription factors. In the liver and small intestines, multiple lncRNAs and TFs showed distinct associations with CYP3A expression, highlighting the contribution of lncRNAs to variability in CYP3A expression.

BIOMEDICINES (2022)

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Article Multidisciplinary Sciences

Upstart DNA sequencers could be a ‘game changer’

Elizabeth Pennisi

SCIENCE (2022)

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Article Health Care Sciences & Services

Validation of Pharmacogenomic Interaction Probability (PIP) Scores in Predicting Drug-Gene, Drug-Drug-Gene, and Drug-Gene-Gene Interaction Risks in a Large Patient Population

Kristine Ashcraft et al.

Summary: This study validated the accuracy of the YouScript(R) PGx interaction probability (PIP) algorithm in predicting drug-gene interactions. The results showed a significant concordance between the PIP scores generated by the algorithm and the actual drug-gene interactions identified through gene panel testing.

JOURNAL OF PERSONALIZED MEDICINE (2022)

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Review Biotechnology & Applied Microbiology

Targeting KRASG12C-Mutated Advanced Colorectal Cancer: Research and Clinical Developments

[Anonymous]

Summary: Identifying mutations in the KRAS gene is crucial for the treatment of colorectal cancer. The introduction of KRAS(G12C) inhibitors has shown safety and efficacy in preclinical studies and early phase trials, although not all tumor types with KRAS(G12C) mutations are responsive to monotherapy. Colorectal cancer patients have shown less benefit, possibly due to treatment-induced resistance through increased EGFR signaling. Combination therapy trials with EGFR inhibitors are currently underway.

ONCOTARGETS AND THERAPY (2022)

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Review Pharmacology & Pharmacy

Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity

Qinglian Zhai et al.

Summary: CYP3A enzymes play a crucial role in the metabolism of drugs used in clinical practice. Genetic factors have been shown to contribute significantly to the variability in CYP3A4 activity. However, the complex nature of the CYP3A locus has hindered the identification and clinical application of genetic variants compared to other Cytochrome P450 enzymes. Recent evidence suggests that low frequency genetic variations account for a substantial portion of the missing heritability. This review provides an overview of the current pharmacogenomics knowledge of CYP3A activity and discusses potential future directions for improving our understanding of CYP3A variability.

FRONTIERS IN PHARMACOLOGY (2022)

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Article Pharmacology & Pharmacy

Characterization of ADME Gene Variation in Colombian Population by Exome Sequencing

Daniel Felipe Silgado-Guzman et al.

Summary: This study investigated the genetic variability of drug-related genes in a Colombian population using whole-exome sequencing. The findings suggest that rare genetic variants play a significant role in interindividual variability in drug response. Additionally, the genetic frequencies in the Colombian population differed from other Latin-American populations.

FRONTIERS IN PHARMACOLOGY (2022)

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Review Genetics & Heredity

Artificial Intelligence, Healthcare, Clinical Genomics, and Pharmacogenomics Approaches in Precision Medicine

Habiba Abdelhalim et al.

Summary: Precision medicine uses clinical and genomic data to improve health outcomes for chronic diseases. It considers individual differences in treatment response and integrates knowledge from various fields to personalize treatments and predict diseases.

FRONTIERS IN GENETICS (2022)

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Article Psychology, Biological

Rare genetic variants explain missing heritability in smoking

Seon-Kyeong Jang et al.

Summary: Rare genetic variants contribute significantly to the heritability of smoking behavior.

NATURE HUMAN BEHAVIOUR (2022)

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Article Oncology

APOBEC mutagenesis, kataegis, chromothripsis in EGFR-mutant osimertinib-resistant lung adenocarcinomas

P. Selenica et al.

Summary: This study found that APOBEC mutational signatures increase in EGFR-mutant lung cancer under the selective pressure of osimertinib. Samples with APOBEC mutational signatures had increased mutation frequency, more frequent occurrence of private mutations and large-scale genomic alterations.

ANNALS OF ONCOLOGY (2022)

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Review Genetics & Heredity

APOBEC-Induced Mutagenesis in Cancer

Tony M. Mertz et al.

Summary: The occurrence and development of cancer are closely related to mutations, and dysregulated activity of APOBECs can lead to mutations. The study of mutation signatures helps us understand the patterns and processes of mutations. In humans, APOBEC-generated genetic heterogeneity plays an important role in cancer development, metastasis, and resistance to therapy.

ANNUAL REVIEW OF GENETICS (2022)

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Article Medicine, Research & Experimental

Regulatory variants in a novel distal enhancer regulate the expression of CYP3A4 and CYP3A5

Joseph M. Collins et al.

Summary: The cytochrome P450 3A genes are highly expressed in the liver and play a crucial role in metabolizing commonly prescribed medications. This study identified a regulatory region that interacts with the promoter of CYP3A4 gene, and demonstrated its role as a shared enhancer for regulating the expression of three CYP3A genes. Furthermore, two genetic variants were identified to be associated with increased expression of CYP3A4 and CYP3A5, and these variants showed potential clinical relevance in predicting drug response and treatment outcomes.

CTS-CLINICAL AND TRANSLATIONAL SCIENCE (2022)

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Review Neurosciences

Somatic Mutations and Alzheimer's Disease

[Anonymous]

Summary: Alzheimer's disease is a global health challenge, and besides proteinopathy, the diversity of the genome and somatic mutations are also associated with the disease. Triggering events are required for Alzheimer's disease to occur. Artificial intelligence and big data have potential roles in identifying causal somatic mutation markers and drug development.

JOURNAL OF ALZHEIMERS DISEASE (2022)

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Review Oncology

Liquid biopsy: current technology and clinical applications

Mina Nikanjam et al.

Summary: Liquid biopsies, including circulating extracellular nucleic acids (cfDNA and ctDNA) and circulating tumor cells (CTCs), have important clinical applications in precision oncology, such as predicting treatment response and resistance, analyzing prognosis and tumor burden, and detecting cancer at early stages. This review provides an overview of current technologies and clinical applications for liquid biopsies, highlighting the potential of this powerful tool in multiple aspects of cancer management.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Review Oncology

Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective From the International Association for the Study of Lung Cancer Pathology Committee

Mari Mino-Kenudson et al.

Summary: Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has become the main treatment for advanced lung cancers. However, only a subset of patients respond to ICIs. The use of programmed death-ligand 1 (PD-L1) protein expression and tumor mutational burden (TMB) as predictive biomarkers has limitations. Ongoing research aims to find better immunotherapy biomarkers for treatment response and prognosis.

JOURNAL OF THORACIC ONCOLOGY (2022)

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Article Genetics & Heredity

The genetic landscape of major drug metabolizing cytochrome P450 genes-an updated analysis of population-scale sequencing data

Yitian Zhou et al.

Summary: This study updates the distribution of CYP gene alleles using large-scale sequencing data, and reveals the contribution of uncharacterized rare alleles to genetic variability. By translating the sequencing data into population-specific metabolizer phenotype patterns, it provides a relevant resource for optimizing genotyping strategies and precision public health.

PHARMACOGENOMICS JOURNAL (2022)

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Editorial Material Multidisciplinary Sciences

Exclusion cycles: Reinforcing disparities in medicine

Ana Bracic et al.

SCIENCE (2022)

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Article Multidisciplinary Sciences

Molecular structures reveal synergistic rescue of Δ508 CFTR by Trikafta modulators

Karol Fiedorczuk et al.

SCIENCE (2022)

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Article Multidisciplinary Sciences

Functional regulatory variants implicate distinct transcriptional networks in dementia

Yonatan A. Cooper et al.

Summary: Predicting the function of noncoding variation remains a major challenge in modern genetics. This study utilized massively parallel reporter assays to identify functional regulatory variants linked to Alzheimer's disease and progressive supranuclear palsy. The research showed that noncoding genetic risk is driven by common genetic variants through their aggregate activity on specific transcriptional programs.

SCIENCE (2022)

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Article Biochemistry & Molecular Biology

Pharmacogenomic Profiling of Cisplatin-Resistant and -Sensitive Human Osteosarcoma Cell Lines by Multimodal Targeted Next Generation Sequencing

Claudia Maria Hattinger et al.

Summary: This study investigated the relationship between SNPs and CDDP resistance in high-grade osteosarcoma cells, providing a basis for further research on the topic.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Oncology

Therapeutic advances in metastatic pancreatic cancer: a focus on targeted therapies

Anthony Turpin et al.

Summary: Mortality from pancreatic ductal adenocarcinoma is increasing worldwide and there is an urgent need for effective new treatments. The current treatment for fit patients with metastatic PDAC is based on two chemotherapy combinations that were validated more than 8 years ago. Although treatments targeting specific molecular alterations have largely failed in unselected patients, encouraging results have been observed in subpopulations with certain mutations or gene fusions. Targeted tumor metabolism therapies and immunotherapy have been disappointing but are still being investigated in combination with other drugs. Optimizing pharmacokinetics and adapting available chemotherapies based on molecular signatures are promising avenues of research. Continuous search for actionable vulnerabilities in PDAC tumor cells and microenvironments may lead to more personalized therapeutic approaches.

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY (2022)

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Article Computer Science, Artificial Intelligence

The All of Us Research Program: Data quality, utility, and diversity

Andrea H. Ramirez et al.

Summary: The All of Us Research Program aims to democratize access to analytical tools and participant information through a cloud-based Researcher Workbench, advancing precision medicine research. Validation study findings demonstrate the successful replication of various complex diseases in 315,000 participants and the inclusion of historically underrepresented groups in biomedical research.

PATTERNS (2022)

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Review Oncology

Cancer proteogenomics: current impact and future prospects

D. R. Mani et al.

Summary: Genomic analyses have greatly impacted cancer research by identifying driver mutations and developing targeted therapies. However, the functions of most somatic mutations and copy number variants in tumors remain unknown. Proteogenomics, which integrates proteins and their modifications with genomic data, has emerged as a new field and is providing valuable insights into malignant transformation and therapeutic outcomes.

NATURE REVIEWS CANCER (2022)

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Article Biochemistry & Molecular Biology

CASPIAN: A method to identify chromatin topological associated domains based on spatial density cluster q

Haiyan Gong et al.

Summary: CASPIAN is a method based on spatial density clustering algorithm for accurately identifying chromatin TAD boundaries and enriching factors related to gene expression. It is implemented using HDBSCAN and adapts well to Hi-C contact matrices of different resolutions.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2022)

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Article Biochemistry & Molecular Biology

Common genetic substrates of alcohol and substance use disorder severity revealed by pleiotropy detection against GWAS catalog in two populations

Qian Peng et al.

Summary: The study investigates the genetic associations of alcohol and other substance use disorders and identifies potential pleiotropic gene variants using a machine learning approach. Differences in the expression and regulation of pleiotropic genes for different substance use disorders in different populations highlight the complexity of genetic factors involved in these disorders.

ADDICTION BIOLOGY (2021)

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Article Oncology

Pathological Tumor Response Following Immune Checkpoint Blockade for Deficient Mismatch Repair Advanced Colorectal Cancer

Kaysia Ludford et al.

Summary: This study found that residual radiographic tumor following anti-PD1 therapy may not require systematic resection and pathological complete response may be feasible for dMMR mCRC patients. Further larger prospective studies are needed to confirm these findings.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2021)

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Review Pharmacology & Pharmacy

Warfarin dosing algorithms: A systematic review

Innocent G. Asiimwe et al.

Summary: The review examined various warfarin dosing algorithms across different populations, showing that most algorithms are developed for Asians and Whites, with limited external validation and assessment for clinical utility. Recommendations were made to prioritize under-represented populations in algorithm development and assessment to improve reliability and applicability.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2021)

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Article

Proactive versus Reactive Therapeutic Drug Monitoring: Why, When, and How?

Manar Shmais et al.

Inflammatory Intestinal Diseases (2021)

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Review Oncology

50th anniversary of the first clinical trial with ICI 46,474 (tamoxifen): then what happened?

V. Craig Jordan

Summary: Following the approval of oral contraceptives, the pharmaceutical industry sought new opportunities for reproductive regulation, leading to the discovery of the compound ICI 46,474 for the treatment of breast cancer. Despite initial patent setbacks in the USA, tamoxifen eventually found success in treating breast cancer, becoming a major advancement in cancer therapy.

ENDOCRINE-RELATED CANCER (2021)

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Review Medicine, General & Internal

Considerations When Applying Pharmacogenomics to Your Practice

Wayne T. Nicholson et al.

Summary: The study found that the application of pharmacogenomics is essential for clinicians who have not received education in this field, with some differences from traditional drug interactions. National and international consortium guidelines can better assist clinicians in applying pharmacogenomics in practice.

MAYO CLINIC PROCEEDINGS (2021)

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Review Biochemistry & Molecular Biology

Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives

Svetlana N. Aleksakhina et al.

Summary: The administration of many cancer drugs is tailored to genetic tests, leading to personalized treatment plans which have significantly improved disease outcomes for a large portion of cancer patients. Genetic testing is now widely used in clinical practice and plays a crucial role in guiding treatment decisions.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

Cytochrome P450 Enzymes and Drug Metabolism in Humans

Mingzhe Zhao et al.

Summary: Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play crucial roles in drug detoxification, cellular metabolism, and homeostasis. In addition to their basic metabolic functions, CYPs can also influence drug responses by affecting drug action, safety, bioavailability, and drug resistance through metabolism.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Oncology

Applications and challenges in therapeutic drug monitoring of cancer treatment: A review

Bushra Salman et al.

Summary: Most anticancer agents exhibit wide variability in pharmacokinetics and have a narrow therapeutic index, making fixed dosing suboptimal. While using pharmacokinetic or therapeutic drug monitoring-guided dosing may achieve best therapeutic outcomes, challenges arise from multiple factors contributing to pharmacokinetic variability. Standard guidelines for pharmacokinetic-guided dosing are lacking for most agents, emphasizing the importance of understanding factors contributing to pharmacokinetic variability for dose individualization.

JOURNAL OF ONCOLOGY PHARMACY PRACTICE (2021)

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Article Cell Biology

Drivers of dynamic intratumor heterogeneity and phenotypic plasticity

Antara Biswas et al.

Summary: Cancer is a clonal disease with intratumor heterogeneity, where tumor cells have genetic and nongenetic variations contributing to cell state transition and phenotypic heterogeneity. Dynamic heterogeneity and phenotypic plasticity can lead to resistance to treatment, metastasis, and evolvability in cancer.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2021)

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Article Oncology

PD-L1 polymorphisms predict survival outcomes in advanced non-small-cell lung cancer patients treated with PD-1 blockade

Hironori Yoshida et al.

Summary: The study found that PD-L1 polymorphisms were associated with overall survival in NSCLC patients treated with nivolumab, suggesting they could be useful predictive biomarkers.

EUROPEAN JOURNAL OF CANCER (2021)

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Article Multidisciplinary Sciences

Exome sequencing and analysis of 454,787 UK Biobank participants

Joshua D. Backman et al.

Summary: In this study, whole-exome sequencing was used to identify gene-trait associations in 454,787 individuals, revealing 564 distinct genes with significant trait associations. Rare variant associations were enriched in loci from genome-wide association studies (GWAS) but most were independent of common variant signals.

NATURE (2021)

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Article Chemistry, Medicinal

A Decade of FDA-Approved Drugs (2010-2019): Trends and Future Directions

Dean G. Brown et al.

Summary: Evaluation of 378 novel drugs and 27 biosimilars approved by the U.S. FDA between 2010 and 2019 revealed oncology as the top therapy area, potential increase in clinical development times, and rapid progress in innovation in new modalities.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Genetics & Heredity

CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice

Daniel Carranza-Leon et al.

Summary: This study found a correlation between CYP2D6 metabolizer status and pain response to codeine treatment. Poor/intermediate metabolizers had lower odds of achieving a pain response. Combining CYP2D6 phenotype and clinical variables can help discriminate between responders and nonresponders to codeine treatment.

PHARMACOGENOMICS JOURNAL (2021)

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Review Genetics & Heredity

A systematic review and meta-analysis of genotype-based and individualized data analysis of SLCO1B1 gene and statin-induced myopathy

Saowalak Turongkaravee et al.

Summary: This meta-analysis revealed a significant association between rs4149056 polymorphism in the SLCO1B1 gene and the risk of myopathy in statin users, particularly in Caucasians. However, rs2306283 polymorphism did not show a significant association with myopathy risk in Caucasians and Asians. No publication bias was detected for both polymorphisms.

PHARMACOGENOMICS JOURNAL (2021)

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News Item Multidisciplinary Sciences

BIOMEDICINE NIH's 'precision nutrition' bet aims for individualized diets

Jocelyn Kaiser

SCIENCE (2021)

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Editorial Material Multidisciplinary Sciences

Modulating gut microbiota to treat cancer

Christopher H. Woelk et al.

SCIENCE (2021)

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Article Clinical Neurology

Genome-wide epistasis analysis for Alzheimer's disease and implications for genetic risk prediction

Hui Wang et al.

Summary: This study conducted a genome-wide epistasis analysis to identify novel genetic interactions potentially involved in Alzheimer's disease, and developed a new method to assess the genetic risk of AD. The findings suggest that Epistasis Risk Scores (ERS) can serve as an indicator for genetic risk of AD.

ALZHEIMERS RESEARCH & THERAPY (2021)

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Article Biology

Transcriptome annotation in the cloud: complexity, best practices, and cost

Roberto Vera Alvarez et al.

Summary: The researchers compared multiple BLAST sequence alignments using AWS and GCP and found that public cloud providers are a practical and cost-effective alternative for conducting advanced computational biology experiments. Their study aimed to establish an estimate of the cost and compute time needed for the execution of multiple BLAST runs in a cloud environment.

GIGASCIENCE (2021)

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Article Health Care Sciences & Services

Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000-2020)

Jeeyun A. Kim et al.

Summary: Pharmacogenomics (PGx) is a key component of precision medicine that analyzes genetic variations to tailor drug therapies. This study found that the proportion of new drugs approved by the US FDA with PGx information has been increasing, especially in the field of cancer therapies. Results show that PGx information in cancer drugs is more clinically actionable compared to other therapeutic areas, indicating the need for more evidence to support the clinical adoption of pharmacogenomics in non-cancer treatments.

JOURNAL OF PERSONALIZED MEDICINE (2021)

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Review Oncology

Applications of Multi-omics Approaches for Exploring the Molecular Mechanism of Ovarian Carcinogenesis

Miaomiao Ye et al.

Summary: Ovarian cancer ranks as the fifth most common cause of cancer-related death in females. Multi-omics approaches have been applied to determine the mechanisms of ovarian oncogenesis at different levels and have identified potential diagnostic and prognostic biomarkers and therapeutic targets. The discovery of molecular signatures and targeted therapy strategies could significantly improve the prognosis of ovarian cancer patients.

FRONTIERS IN ONCOLOGY (2021)

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Review Biochemistry & Molecular Biology

The Role of Omics Approaches to Characterize Molecular Mechanisms of Rare Ovarian Cancers: Recent Advances and Future Perspectives

Yashwanth Subbannayya et al.

Summary: Rare ovarian cancers have a low incidence rate and poor prognosis; exploring their molecular mechanisms is challenging due to their rarity and fragmented research efforts; omics approaches offer detailed insights into the underlying mechanisms and potential biomarkers for diagnosis and treatment.

BIOMEDICINES (2021)

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Review Cardiac & Cardiovascular Systems

Pharmacogenetics to guide cardiovascular drug therapy

Julio D. Duarte et al.

Summary: This Review examines the evidence supporting pharmacogenetic testing in cardiovascular medicine, including data from clinical trials, and provides examples of clinical implementation of genotype-guided cardiovascular therapies. Opportunities for future growth of the field are also discussed.

NATURE REVIEWS CARDIOLOGY (2021)

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Review Oncology

Detection of Microsatellite Instability: State of the Art and Future Applications in Circulating Tumour DNA (ctDNA)

Pauline Gilson et al.

Summary: Microsatellite instability (MSI) is a molecular marker for defects in the mismatch repair system (dMMR) and is linked to higher cancer risk. MSI tumors show mutations throughout the genome, with a focus on microsatellite (MS) DNA repeat sequences. Assessment of MSI/dMMR status is commonly done with immunohistochemistry or PCR, but newer methods based on tumor tissue or plasma samples are emerging trends.

CANCERS (2021)

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Article Oncology

FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden-High Solid for Tumors

Leigh Marcus et al.

Summary: The FDA approved pembrolizumab for the treatment of TMB-H solid tumors in adults and children, based on its significant overall response rate and duration in clinical trials. This marks the first FDA approval of a cancer treatment based on TMB, and the fourth based on a biomarker rather than primary site.

CLINICAL CANCER RESEARCH (2021)

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Article Medicine, General & Internal

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer

Oliver Sartor et al.

Summary: The radioligand therapy with Lu-177-PSMA-617 prolonged both imaging-based progression-free survival and overall survival in patients with PSMA-positive metastatic castration-resistant prostate cancer when added to standard care. Adverse events were more common with Lu-177-PSMA-617 but did not significantly impact quality of life.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Genetics & Heredity

The Role of Mitochondrial DNA Variation in Drug Response: A Systematic Review

Samantha W. Jones et al.

Summary: The triad of drug efficacy, toxicity and resistance is crucial in determining the risk-benefit balance of therapeutics. Pharmacogenomics can potentially improve this balance by stratifying patient populations based on DNA variants. Research on the impact of mitochondrial DNA variation on drug response is still inconclusive and further studies are needed to explain the variability in drug response.

FRONTIERS IN GENETICS (2021)

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Review Oncology

Combination Strategies to Augment Immune Check Point Inhibitors Efficacy-Implications for Translational Research

Hrishi Varayathu et al.

Summary: Immune checkpoint inhibitor therapy has revolutionized cancer immunotherapy, but not all patients respond to it. Current research is focused on combining immune checkpoint inhibitors with other drugs to explore more effective therapeutic strategies.

FRONTIERS IN ONCOLOGY (2021)

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Review Oncology

ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer

Jamie O. Brett et al.

Summary: ESR1 mutations play a crucial role in breast cancer treatment, affecting tumor sensitivity to therapies. These mutations influence resistance in estrogen receptor-targeting and combination therapies, requiring further research for better understanding and treatment strategies.

BREAST CANCER RESEARCH (2021)

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Review Biotechnology & Applied Microbiology

In SilicoTools and Approaches for the Prediction of Functional and Structural Effects of Single-Nucleotide Polymorphisms on Proteins: An Expert Review

Metin Yazar et al.

Summary: This expert review discusses in silico tools and algorithms for predicting the functional or structural effects of SNP variants, as well as describing the phenotypic effects of nsSNPs on protein structure, the association between pathogenicity of variants, and the functional or structural features of disease-associated variants. Case studies investigating the functional and structural effects of nsSNPs on selected protein structures are highlighted, and it is concluded that creating a consistent workflow with a combination of in silico approaches or tools should be considered to improve the performance, accuracy, and precision of biological and clinical predictions made in silico.

OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY (2021)

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Review Pharmacology & Pharmacy

Drugs and hepatic transporters: A review

Alexander Jetter et al.

PHARMACOLOGICAL RESEARCH (2020)

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Article Medical Laboratory Technology

Cancer Chemotherapy: The Case for Therapeutic Drug Monitoring

Claire E. Knezevic et al.

THERAPEUTIC DRUG MONITORING (2020)

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Article Oncology

Routine Plasma-Based Genotyping to Comprehensively Detect Germline, Somatic, and Reversion BRCA Mutations among Patients with Advanced Solid Tumors

Neelima Vidula et al.

CLINICAL CANCER RESEARCH (2020)

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Review Pharmacology & Pharmacy

Study of pharmacogenomic information in FDA-approved drug labeling to facilitate application of precision medicine

Darshan Mehta et al.

DRUG DISCOVERY TODAY (2020)

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Review Oncology

PD-L1 Testing for Lung Cancer in 2019: Perspective From the IASLC Pathology Committee

Sylvie Lantuejoul et al.

JOURNAL OF THORACIC ONCOLOGY (2020)

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Review Genetics & Heredity

Drug-drug-gene interactions and adverse drug reactions

Mustafa Adnan Malki et al.

PHARMACOGENOMICS JOURNAL (2020)

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Review Oncology

Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen

Carmen W. H. Chan et al.

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY (2020)

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Article Economics

Use of Real-World Evidence in US Payer Coverage Decision-Making for Next-Generation Sequencing-Based Tests: Challenges, Opportunities, and Potential Solutions

Patricia A. Deverka et al.

VALUE IN HEALTH (2020)

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Article Biotechnology & Applied Microbiology

Cis-acting regulatory elements regulating CYP3A4 transcription in human liver

Joseph M. Collins et al.

PHARMACOGENETICS AND GENOMICS (2020)

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Review Biochemistry & Molecular Biology

Pharmacogenetic factors affecting β-blocker metabolism and response

Cameron D. Thomas et al.

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY (2020)

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Editorial Material Genetics & Heredity

Pharmacogenomics and Personalized Medicine

Erika Cecchin et al.

GENES (2020)

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Review Oncology

The Promises and Challenges of Tumor Mutation Burden as an Immunotherapy Biomarker: A Perspective from the International Association for the Study of Lung Cancer Pathology Committee

Lynette Sholl et al.

JOURNAL OF THORACIC ONCOLOGY (2020)

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Article Oncology

Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study

Susan M. Domchek et al.

LANCET ONCOLOGY (2020)

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Article Biochemistry & Molecular Biology

Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing

Ashley Maynard et al.

CELL (2020)

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Article Multidisciplinary Sciences

Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy

Lukas F. Mager et al.

SCIENCE (2020)

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Review Oncology

Clinical assays for assessment of homologous recombination DNA repair deficiency

Elizabeth H. Stover et al.

GYNECOLOGIC ONCOLOGY (2020)

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Article Oncology

Clinical BRCA1/2 Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance

Stephen J. Pettitt et al.

CANCER DISCOVERY (2020)

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Article Multidisciplinary Sciences

The GTEx Consortium atlas of genetic regulatory effects across human tissues

Francois Aguet et al.

SCIENCE (2020)

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Review Oncology

Poly(ADP-Ribose) Polymerase Inhibitors in Prostate Cancer: Molecular Mechanisms, and Preclinical and Clinical Data

Dawid Sigorski et al.

TARGETED ONCOLOGY (2020)

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Review Medicine, General & Internal

Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review

Sylvia D. Klomp et al.

JOURNAL OF CLINICAL MEDICINE (2020)

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Review Oncology

Application of pharmacogenetics in oncology

Nelly N. Miteva-Marcheva et al.

BIOMARKER RESEARCH (2020)

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Review Genetics & Heredity

Cyp2C19*2 Polymorphism Related to Clopidogrel Resistance in Patients With Coronary Heart Disease, Especially in the Asian Population: A Systematic Review and Meta-Analysis

Ying Sun et al.

FRONTIERS IN GENETICS (2020)

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Review Oncology

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group

F. Mosele et al.

ANNALS OF ONCOLOGY (2020)

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Review Immunology

Combined Anti-Cancer Strategies Based on Anti-Checkpoint Inhibitor Antibodies

Josee Golay et al.

ANTIBODIES (2020)

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Article Biotechnology & Applied Microbiology

CYP2D6 haplotypes with enhancer single-nucleotide polymorphism rs5758550 and rs16947 (*2 allele): implications for CYP2D6 genotyping panels

Balmiki Ray et al.

PHARMACOGENETICS AND GENOMICS (2019)

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Review Pharmacology & Pharmacy

The role of pharmacogenomics in adverse drug reactions

Ramon Cacabelos et al.

EXPERT REVIEW OF CLINICAL PHARMACOLOGY (2019)

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Review Oncology

ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach

C. Luchini et al.

ANNALS OF ONCOLOGY (2019)

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Review Gastroenterology & Hepatology

Therapeutic drug monitoring in inflammatory bowel disease: for every patient and every drug?

Konstantinos Papamichael et al.

CURRENT OPINION IN GASTROENTEROLOGY (2019)

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Article Oncology

A Practical Guide for the Follow-Up of Patients with Advanced Basal Cell Carcinoma During Treatment with Hedgehog Pathway Inhibitors

Clio Dessinioti et al.

ONCOLOGIST (2019)

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Article Medicine, Research & Experimental

Precision Medicines' Impact on Orphan Drug Designation

Christine M. Mueller et al.

CTS-CLINICAL AND TRANSLATIONAL SCIENCE (2019)

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Editorial Material Genetics & Heredity

Priority index for human genetics and drug discovery

Robert M. Plenge

NATURE GENETICS (2019)

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Article Medicine, General & Internal

Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma

C. Robert et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Article Medicine, General & Internal

Pharmacogenomics

Dan M. Roden et al.

LANCET (2019)

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Review Psychiatry

Pharmacogenetics and Depression: A Critical Perspective

Filippo Corponi et al.

PSYCHIATRY INVESTIGATION (2019)

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Review Oncology

How liquid biopsies can change clinical practice in oncology

G. Siravegna et al.

ANNALS OF ONCOLOGY (2019)

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Review Oncology

Sonic Hedgehog Pathway Inhibition in the Treatment of Advanced Basal Cell Carcinoma

Erica Leavitt et al.

CURRENT TREATMENT OPTIONS IN ONCOLOGY (2019)

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Review Immunology

The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

Weiting Qin et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Review Oncology

Prognostic and predictive biomarkers in breast cancer: Past, present and future

Andrea Nicolini et al.

SEMINARS IN CANCER BIOLOGY (2018)

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Review Oncology

Perspective: APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution

S. Venkatesan et al.

ANNALS OF ONCOLOGY (2018)

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Review Pharmacology & Pharmacy

Cytochrome P450 Structure, Function and Clinical Significance: A Review

Palrasu Manikandan et al.

CURRENT DRUG TARGETS (2018)

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Review Pathology

Clinical pharmacogenomics testing in the era of next generation sequencing: challenges and opportunities for precision medicine

Yuan Ji et al.

EXPERT REVIEW OF MOLECULAR DIAGNOSTICS (2018)

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Review Cardiac & Cardiovascular Systems

The Pharmacologic Role and Clinical Utility of PCSK9 Inhibitors for the Treatment of Hypercholesterolemia

C. Michael White

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS (2018)

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Article Oncology

Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer

Michael J. Overman et al.

JOURNAL OF CLINICAL ONCOLOGY (2018)

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Article Oncology

Combined BRAF, EGFR, and MEK Inhibition in Patients with &ITBRAF&ITV600E-Mutant Colorectal Cancer

Ryan B. Corcoran et al.

CANCER DISCOVERY (2018)

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Article Multidisciplinary Sciences

Deoxycholic acid supplementation impairs glucose homeostasis in mice

Karolina E. Zaborska et al.

PLOS ONE (2018)

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Article Biotechnology & Applied Microbiology

Combined genetic influence of the nicotinic receptor gene cluster CHRNA5/A3/B4 on nicotine dependence

Sung-Ha Lee et al.

BMC GENOMICS (2018)

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Article Cardiac & Cardiovascular Systems

Interactions Between Regulatory Variants in CYP7A1 (Cholesterol 7 alpha-Hydroxylase) Promoter and Enhancer Regions Regulate CYP7A1 Expression

Danxin Wang et al.

CIRCULATION-GENOMIC AND PRECISION MEDICINE (2018)

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Article Genetics & Heredity

Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC)

Kelly E. Caudle et al.

GENETICS IN MEDICINE (2017)

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Article Genetics & Heredity

The CHRNA5/CHRNA3/CHRNB4 Nicotinic Receptor Regulome: Genomic Architecture, Regulatory Variants, and Clinical Associations

Elizabeth S. Barrie et al.

HUMAN MUTATION (2017)

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Review Genetics & Heredity

Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses

J. M. Campbell et al.

PHARMACOGENOMICS JOURNAL (2017)

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Review Biochemical Research Methods

Proteogenomic studies on cancer drug resistance: towards biomarker discovery and target identification

Shuyue Fu et al.

EXPERT REVIEW OF PROTEOMICS (2017)

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Article Medicine, General & Internal

Pharmacogenomics: Precision Medicine and Drug Response

Richard M. Weinshilboum et al.

MAYO CLINIC PROCEEDINGS (2017)

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Article Multidisciplinary Sciences

Genetic effects on gene expression across human tissues

Francois Aguet et al.

NATURE (2017)

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Article Biotechnology & Applied Microbiology

Trends in GPCR drug discovery: new agents, targets and indications

Alexander S. Hauser et al.

NATURE REVIEWS DRUG DISCOVERY (2017)

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Article Chemistry, Multidisciplinary

Network Reconstruction Reveals that Valproic Acid Activates Neurogenic Transcriptional Programs in Adult Brain Following Traumatic Injury

Gerald A. Higgins et al.

PHARMACEUTICAL RESEARCH (2017)

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Review Pharmacology & Pharmacy

Pharmacogenetics of drug-drug interaction and drug-drug-gene interaction: a systematic review on CYP2C9, CYP2C19 and CYP2D6

Muh Akbar Bahar et al.

PHARMACOGENOMICS (2017)

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Article Multidisciplinary Sciences

Deriving genomic diagnoses without revealing patient genomes

Karthik A. Jagadeesh et al.

SCIENCE (2017)

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Article Oncology

Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Olga Kondrashova et al.

CANCER DISCOVERY (2017)

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Article Oncology

Analysis of Circulating Cell-Free DnA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors

David Quigley et al.

CANCER DISCOVERY (2017)

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Article Oncology

Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition

Jane Goodall et al.

CANCER DISCOVERY (2017)

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Article Oncology

Diverse BRCA1 and BRCA2 Reversion Mutations in Circulating Cell-Free DNA of Therapy-Resistant Breast or Ovarian Cancer

Britta Weigelt et al.

CLINICAL CANCER RESEARCH (2017)

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Article Biochemistry & Molecular Biology

Advances in understanding tumour evolution through single-cell sequencing

Jack Kuipers et al.

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER (2017)

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Article Pharmacology & Pharmacy

Integrating pharmacogenomics into electronic health records with clinical decision support

J. Kevin Hicks et al.

AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY (2016)

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Review Nutrition & Dietetics

Variation in the Ability to Taste Bitter Thiourea Compounds: Implications for Food Acceptance, Dietary Intake, and Obesity Risk in Children

Kathleen L. Keller et al.

ANNUAL REVIEW OF NUTRITION, VOL 36 (2016)

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Article Biochemical Research Methods

Evaluating tools for transcription factor binding site prediction

Narayan Jayaram et al.

BMC BIOINFORMATICS (2016)

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Article Pharmacology & Pharmacy

History of Orphan Drug Regulation-United States and Beyond

M. E. Haffner

CLINICAL PHARMACOLOGY & THERAPEUTICS (2016)

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Editorial Material Medicine, General & Internal

Data Sharing An Ethical and Scientific Imperative

Howard Bauchner et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2016)

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Article Neurosciences

Predicting drug-induced QT prolongation and torsades de pointes

Dan M. Roden

JOURNAL OF PHYSIOLOGY-LONDON (2016)

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Article Oncology

Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial

David Planchard et al.

LANCET ONCOLOGY (2016)

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Review Biochemistry & Molecular Biology

Next generation sequencing: implications in personalized medicine and pharmacogenomics

Bahareh Rabbani et al.

MOLECULAR BIOSYSTEMS (2016)

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Article Genetics & Heredity

NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity

Takaya Moriyama et al.

NATURE GENETICS (2016)

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Article Multidisciplinary Sciences

Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients

Jacob J. Chabon et al.

NATURE COMMUNICATIONS (2016)

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Article Cardiac & Cardiovascular Systems

Effect of genetic variations on ticagrelor plasma levels and clinical outcomes

Christoph Varenhorst et al.

EUROPEAN HEART JOURNAL (2015)

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Review Multidisciplinary Sciences

Pharmacogenomics in the clinic

Mary V. Relling et al.

NATURE (2015)

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Article Medicine, General & Internal

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

D. T. Le et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

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Article Multidisciplinary Sciences

Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms

Roshan Mascarenhas et al.

PLOS ONE (2015)

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Article Genetics & Heredity

A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism

Anu Loukola et al.

PLOS GENETICS (2015)

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Editorial Material Medicine, General & Internal

UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

Cathie Sudlow et al.

PLOS MEDICINE (2015)

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Review Allergy

Genetics of Immune-Mediated Adverse Drug Reactions: a Comprehensive and Clinical Review

V. L. M. Yip et al.

CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY (2015)

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Review Genetics & Heredity

Progress towards the integration of pharmacogenomics in practice

Sean D. Mooney

HUMAN GENETICS (2015)

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Article Biochemistry & Molecular Biology

Functional characterization of CYP2D6 enhancer polymorphisms

Danxin Wang et al.

HUMAN MOLECULAR GENETICS (2015)

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Review Biochemistry & Molecular Biology

Development and Applications of CRISPR-Cas9 for Genome Engineering

Patrick D. Hsu et al.

CELL (2014)

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Review Pharmacology & Pharmacy

Functional Gene Variants of CYP3A4

A. N. Werk et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2014)

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Article Biochemistry & Molecular Biology

Genome-wide map of regulatory interactions in the human genome

Nastaran Heidari et al.

GENOME RESEARCH (2014)

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Review Genetics & Heredity

Missing heritability of common diseases and treatments outside the protein-coding exome

Wolfgang Sadee et al.

HUMAN GENETICS (2014)

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Article Biochemistry & Molecular Biology

Common CYP2D6 polymorphisms affecting alternative splicing and transcription: long-range haplotypes with two regulatory variants modulate CYP2D6 activity

Danxin Wang et al.

HUMAN MOLECULAR GENETICS (2014)

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Article Genetics & Heredity

Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans

W. Hernandez et al.

PHARMACOGENOMICS JOURNAL (2014)

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Review Oncology

Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers

Johnathan A. Watkins et al.

BREAST CANCER RESEARCH (2014)

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Article Biotechnology & Applied Microbiology

Whole transcriptome RNA-Seq allelic expression in human brain

Ryan M. Smith et al.

BMC GENOMICS (2013)

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Article Medicine, General & Internal

Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study

Minoli A. Perera et al.

LANCET (2013)

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Article Multidisciplinary Sciences

Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations

Yubo Zhang et al.

NATURE (2013)

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Review Pharmacology & Pharmacy

CYP3A4*22: promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy

Laure Elens et al.

PHARMACOGENOMICS (2013)

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Review Pharmacology & Pharmacy

Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation

Ulrich M. Zanger et al.

PHARMACOLOGY & THERAPEUTICS (2013)

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Letter Dermatology

Initial Assessment of Tumor Regrowth After Vismodegib in Advanced Basal Cell Carcinoma

Anne Lynn S. Chang et al.

ARCHIVES OF DERMATOLOGY (2012)

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Editorial Material Pharmacology & Pharmacy

Pharmacogenomics Knowledge for Personalized Medicine

M. Whirl-Carrillo et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2012)

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Article Biochemistry & Molecular Biology

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM

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MOLECULAR PSYCHIATRY (2012)

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Article Multidisciplinary Sciences

The long-range interaction landscape of gene promoters

Amartya Sanyal et al.

NATURE (2012)

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Article Multidisciplinary Sciences

An integrated encyclopedia of DNA elements in the human genome

Ian Dunham et al.

NATURE (2012)

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Article Medicine, General & Internal

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

Marco Gerlinger et al.

NEW ENGLAND JOURNAL OF MEDICINE (2012)

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Article Medicine, General & Internal

Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer

Jonathan Ledermann et al.

NEW ENGLAND JOURNAL OF MEDICINE (2012)

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Article Pharmacology & Pharmacy

Personalized medicine is more than genomic medicine: confusion over terminology impedes progress towards personalized healthcare

Leigh Ann Simmons et al.

PERSONALIZED MEDICINE (2012)

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Article Biotechnology & Applied Microbiology

Genome-wide association study of plasma efavirenz pharmacokinetics in AIDS Clinical Trials Group protocols implicates several CYP2B6 variants

Emily R. Holzinger et al.

PHARMACOGENETICS AND GENOMICS (2012)

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Article Genetics & Heredity

Mining the Unknown: A Systems Approach to Metabolite Identification Combining Genetic and Metabolic Information

Jan Krumsiek et al.

PLOS GENETICS (2012)

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Review Biochemistry & Molecular Biology

Spreading Chromatin into Chemical Biology

C. David Allis et al.

CHEMBIOCHEM (2011)

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Article Pharmacology & Pharmacy

Pharmacogenomics of the RNA World: Structural RNA Polymorphisms in Drug Therapy

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CLINICAL PHARMACOLOGY & THERAPEUTICS (2011)

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Review Multidisciplinary Sciences

Cancer immunotherapy comes of age

Ira Mellman et al.

NATURE (2011)

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Article Genetics & Heredity

Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs

D. Wang et al.

PHARMACOGENOMICS JOURNAL (2011)

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Review Pharmacology & Pharmacy

Pharmacogenetics, Pharmacogenomics, and Individualized Medicine

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PHARMACOLOGICAL REVIEWS (2011)

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PARP inhibitors: its role in treatment of cancer

Alice Chen

Chinese Journal of Cancer (2011)

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Article Cell Biology

Interfering with Resistance to Smoothened Antagonists by Inhibition of the PI3K Pathway in Medulloblastoma

Silvia Buonamici et al.

SCIENCE TRANSLATIONAL MEDICINE (2010)

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Article Multidisciplinary Sciences

Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution

Sohrab P. Shah et al.

NATURE (2009)

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Article Medicine, General & Internal

Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma.

Daniel D. Von Hoff et al.

NEW ENGLAND JOURNAL OF MEDICINE (2009)

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Article Multidisciplinary Sciences

Potential etiologic and functional implications of genome-wide association loci for human diseases and traits

Lucia A. Hindorff et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

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Article Multidisciplinary Sciences

Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma

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SCIENCE (2009)

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Article Hematology

Regulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement

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BLOOD (2008)

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Article Oncology

Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases

Michael C. Heinrich et al.

CLINICAL CANCER RESEARCH (2008)

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Article Biotechnology & Applied Microbiology

Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes:: detection through allelic expression imbalance in human target tissues

Andrew D. Johnson et al.

PHARMACOGENETICS AND GENOMICS (2008)

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Article Biochemistry & Molecular Biology

v-Src-mediated down-regulation of SSeCKS metastasis suppressor gene promoter by the recruitment of HDAC1 into a USF1-Sp1-Sp3 complex

Yahao Bu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2007)

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Article Pharmacology & Pharmacy

Molecular mechanism of basal CYP3A4 regulation by hepatocyte nuclear factor 4α :: Evidence for direct regulation in the intestine

Heike Tegude et al.

DRUG METABOLISM AND DISPOSITION (2007)

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Article Multidisciplinary Sciences

MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-β-induced collagen expression via inhibition of E-box repressors

Mitsuo Kato et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2007)

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Review Biochemistry & Molecular Biology

Transcriptional regulation and expression of CYP3A4 in hepatocytes

Celia P. Martinez-Jimenez et al.

CURRENT DRUG METABOLISM (2007)

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Article Biochemistry & Molecular Biology

Allelic mRNA expression of X-linked monoamine oxidase a (MAOA) in human brain:: dissection of epigenetic and genetic factors

Julia K. Pinsonneault et al.

HUMAN MOLECULAR GENETICS (2006)

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Article Biotechnology & Applied Microbiology

Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C>T affects mRNA stability

DX Wang et al.

PHARMACOGENETICS AND GENOMICS (2005)

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Article Biotechnology & Applied Microbiology

Impact of the CYP2D6 ultra-rapid metabolizer genotype on doxepin pharmacokinetics and serotonin in platelets

J Kirchheiner et al.

PHARMACOGENETICS AND GENOMICS (2005)

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Review Endocrinology & Metabolism

Strategies and methods for research on sex differences in brain and behavior

JB Becker et al.

ENDOCRINOLOGY (2005)

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Article Anatomy & Morphology

Single base pair change in the long-range Sonic hedgehog limb-specific enhancer is a genetic basis for preaxial polydactyly

SA Maas et al.

DEVELOPMENTAL DYNAMICS (2005)

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Article Pharmacology & Pharmacy

Identification of a novel polymorphic enhancer of the human CYP3A4 gene

K Matsumura et al.

MOLECULAR PHARMACOLOGY (2004)

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Article Oncology

Membrane transporters and channels:: Role of the transportome in cancer chemosensitivity and chemoresistance

Y Huang et al.

CANCER RESEARCH (2004)

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Review Immunology

The three Es of cancer immunoediting

GP Dunn et al.

ANNUAL REVIEW OF IMMUNOLOGY (2004)

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Article Biochemistry & Molecular Biology

Looping and interaction between hypersensitive sites in the active β-globin locus

B Tolhuis et al.

MOLECULAR CELL (2002)

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Article Pharmacology & Pharmacy

Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism

YS Lin et al.

MOLECULAR PHARMACOLOGY (2002)

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Article Multidisciplinary Sciences

Capturing chromosome conformation

J Dekker et al.

SCIENCE (2002)

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Review Medicine, General & Internal

Potential role of pharmacogenomics in reducing adverse drug reactions - A systematic review

KA Phillips et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2001)

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Article Biotechnology & Applied Microbiology

Association of GSTT1 non-null and NAT1 slow/rapid genotypes with von Hippel-Lindau tumour suppressor gene transversions in sporadic renal cell carcinoma

C Gallou et al.

PHARMACOGENETICS (2001)

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Article Genetics & Heredity

Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression

P Kuehl et al.

NATURE GENETICS (2001)

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