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https://www.readbyqxmd.com/read/28921648/rna-therapeutics-in-oncology-advances-challenges-and-future-directions
#1
A Robert MacLeod, Stanley T Crooke
RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28916927/genetic-test-risk-prediction-and-counseling
#2
Maggie Haitian Wang, Haoyi Weng
Advancement in technology has nurtured the new era of genetic tests for personalized medicine. In this chapter, we will introduce the current development, challenges, and the outlook of genetic test, disease risk prediction, and genetic counseling. In the first section, we will present the success cases in the areas of molecular classification of tumors, pharmacogenomics, and Mendelian disorders, and the challenges of genetic tests implementations. In the second section, common methods for genetic risk prediction models and evaluation measures will be introduced, as well as challenges in feature reliability, risk model stability, and clinical utility...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900583/the-daniel-k-inouye-college-of-pharmacy-scripts-precision-medicine-through-the-use-of-pharmacogenomics-current-status-and-barriers-to-implementation
#3
Anita E Ciarleglio, Carolyn Ma
The precision medicine initiative brought forth by President Barack Obama in 2015 is an important step on the journey to truly personalized medicine. A broad knowledge and understanding of the implications of the pharmacogenomic literature will be critical to the achievement of this goal. While a great amount of data has been published in the areas of pharmacogenomics and pharmacogenetics, there are still relatively few instances in which the need for clinical intervention can be stated without doubt, and which are widely accepted and practiced by the medical community...
September 2017: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/28891449/role-of-pharmacogenomics-in-antiepileptic-drug-therapy-current-status-and-future-perspectives
#4
Antonio Gambardella, Angelo Labate, Laura Mumoli, Iscia Lopes-Cendes, Fernando Cendes
BACKGROUND: Growing evidence indicates that pharmacogenomics will positively impact treatment for patients with epilepsy in the near future, leading to the implementation of a precision-based use of antiepileptic drug (AED) therapy, thereby providing a cornerstone for precision medicine. OBJECTIVE: In this review, we briefly summarize the studies of pharmacogenomics in epilepsy, recent advances, and how it may progress in the future. METHODS: We subdivided the review into two main sections: genetic variants that may modulate response to AEDs through pharmacokinetics or pharmacodynamics mechanisms; and gene variants that may affect tolerability and safety of AEDs...
September 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28884473/pharmacotherapy-for-smoking-cessation-effects-by-subgroup-defined-by-genetically-informed-biomarkers
#5
REVIEW
Ewoud Schuit, Orestis A Panagiotou, Marcus R Munafò, Derrick A Bennett, Andrew W Bergen, Sean P David
BACKGROUND: Smoking cessation therapies are not effective for all smokers, and researchers are interested in identifying those subgroups of individuals (e.g. based on genotype) who respond best to specific treatments. OBJECTIVES: To assess whether quit rates vary by genetically informed biomarkers within pharmacotherapy treatment arms and as compared with placebo. To assess the effects of pharmacotherapies for smoking cessation in subgroups of smokers defined by genotype for identified genome-wide significant polymorphisms...
September 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28871186/analysis-of-population-specific-pharmacogenomic-variants-using-next-generation-sequencing-data
#6
Eunyong Ahn, Taesung Park
Functional rare variants in drug-related genes are believed to be highly differentiated between ethnic- or racial populations. However, knowledge of population differentiation (PD) of rare single-nucleotide variants (SNVs), remains widely lacking, with the highest fixation indices, (Fst values), from both rare and common variants annotated to specific genes, having only been marginally used to understand PD at the gene level. In this study, we suggest a new, gene-based PD method, PD of Rare and Common variants (PDRC), for analyzing rare variants, as inspired by Generalized Cochran-Mantel-Haenszel (GCMH) statistics, to identify highly population-differentiated drug response-related genes ("pharmacogenes")...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28867665/pharmacogenomic-variability-of-oral-baclofen-clearance-and-clinical-response-in-children-with-cerebral-palsy
#7
Matthew J McLaughlin, Yang He, Janice Brunstrom-Hernandez, Liu Lin Thio, Bruce C Carleton, Colin J D Ross, Andrea Gaedigk, Andrew Lewandowski, Hongying Dai, William J Jusko, J Steven Leeder
BACKGROUND: Pharmacogenomic variability can contribute to differences in pharmacokinetics and clinical responses. Pediatric patients with cerebral palsy (CP) with genetic variations have not been studied for these potential differences. OBJECTIVE: To determine the genetic sources of variation in oral baclofen clearance and clinical responses. DESIGN: Pharmacogenomic add-on study to determine variability in oral baclofen clearance and clinical responses...
August 31, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28863804/investigation-of-a-gene-signature-to-predict-response-to-immunomodulatory-derivatives-for-patients-with-multiple-myeloma-an-exploratory-retrospective-study-using-microarray-datasets-from-prospective-clinical-trials
#8
Manisha Bhutani, Qing Zhang, Reed Friend, Peter M Voorhees, Lawrence J Druhan, Bart Barlogie, Pieter Sonneveld, Gareth J Morgan, James T Symanowski, Belinda R Avalos, Edward A Copelan, Saad Z Usmani
BACKGROUND: Immunomodulatory derivatives (IMiDs), along with proteasome inhibitors, are key components of treatment regimens for multiple myeloma. Nonetheless, outcomes vary among treated individuals. Drug-specific gene-expression profile (GEP) signatures that aid the prediction of favourable and unfavourable outcomes can provide patients with the most effective therapy for their individual disease. We aimed to develop and validate a gene expression signature to suggest which patients would benefit most from IMiD-based therapies...
September 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28816643/pharmacometabolomics-informs-quantitative-radiomics-for-glioblastoma-diagnostic-innovation
#9
Theodora Katsila, Minos-Timotheos Matsoukas, George P Patrinos, Dimitrios Kardamakis
Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28815128/a-comparative-study-of-different-methods-for-automatic-identification-of-clopidogrel-induced-bleedings-in-electronic-health-records
#10
Hee-Jin Lee, Min Jiang, Yonghui Wu, Christian M Shaffer, John H Cleator, Eitan A Friedman, Joshua P Lewis, Dan M Roden, Josh Denny, Hua Xu
Electronic health records (EHRs) linked with biobanks have been recognized as valuable data sources for pharmacogenomic studies, which require identification of patients with certain adverse drug reactions (ADRs) from a large population. Since manual chart review is costly and time-consuming, automatic methods to accurately identify patients with ADRs have been called for. In this study, we developed and compared different informatics approaches to identify ADRs from EHRs, using clopidogrel-induced bleeding as our case study...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#11
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
September 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28798474/cyp2c19-2-and-cyp2c19-17-variants-and-effect-of-tamoxifen-on-breast-cancer-recurrence-analysis-of-the-international-tamoxifen-pharmacogenomics-consortium-dataset
#12
Per Damkier, Anders Kjærsgaard, Kimberly A Barker, Deidre Cronin-Fenton, Anatasha Crawford, Ylva Hellberg, Emilius A M Janssen, Carl Langefeld, Thomas P Ahern, Timothy L Lash
The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genotype and recurrence of breast cancer. We used outcome and genotyping data from the large publicly available International Tamoxifen Pharmacogenomics Consortium (ITPC) dataset. Cox regression was used to compute the hazard ratios (HRs) for recurrence...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28771511/exploring-public-genomics-data-for-population-pharmacogenomics
#13
Kleanthi Lakiotaki, Alexandros Kanterakis, Evgenia Kartsaki, Theodora Katsila, George P Patrinos, George Potamias
Racial and ethnic differences in drug responses are now well studied and documented. Pharmacogenomics research seeks to unravel the genetic underpinnings of inter-individual variability with the aim of tailored-made theranostics and therapeutics. Taking into account the differential expression of pharmacogenes coding for key metabolic enzymes and transporters that affect drug pharmacokinetics and pharmacodynamics, we advise that data interpretation and analysis need to occur in light of geographical ancestry, if implications for drug development and global health are to be considered...
2017: PloS One
https://www.readbyqxmd.com/read/28768489/improved-anticancer-drug-response-prediction-in-cell-lines-using-matrix-factorization-with-similarity-regularization
#14
Lin Wang, Xiaozhong Li, Louxin Zhang, Qiang Gao
BACKGROUND: Human cancer cell lines are used in research to study the biology of cancer and to test cancer treatments. Recently there are already some large panels of several hundred human cancer cell lines which are characterized with genomic and pharmacological data. The ability to predict drug responses using these pharmacogenomics data can facilitate the development of precision cancer medicines. Although several methods have been developed to address the drug response prediction, there are many challenges in obtaining accurate prediction...
August 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28764766/physicians-pharmacogenomics-information-needs-and-seeking-behavior-a-study-with-case-vignettes
#15
Bret S E Heale, Aly Khalifa, Bryan L Stone, Scott Nelson, Guilherme Del Fiol
BACKGROUND: Genetic testing, especially in pharmacogenomics, can have a major impact on patient care. However, most physicians do not feel that they have sufficient knowledge to apply pharmacogenomics to patient care. Online information resources can help address this gap. We investigated physicians' pharmacogenomics information needs and information-seeking behavior, in order to guide the design of pharmacogenomics information resources that effectively meet clinical information needs...
August 1, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28762370/impact-of-cyp2d6-polymorphisms-on-endoxifen-concentrations-and-breast-cancer-outcomes
#16
REVIEW
G S Hwang, R Bhat, R D Crutchley, M V Trivedi
We investigated the impact of germline CYP2D6 genotyping done using the non-tumor specimen on endoxifen concentrations and/or clinical outcomes in breast cancer (BC) patients treated with tamoxifen in published studies. We evaluated published data from 13 001 patients in 29 studies. Mean±s.d. endoxifen concentrations were significantly lower in poor metabolizers (PM) versus extensive metabolizers (EM) (8.8±7.2 versus 22.3±11.8 ng ml(-1); P<0.05). The PM status did not influence clinical outcomes in majority of the studies...
August 1, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28730340/cyp2d6-genotype-is-not-associated-with-survival-in-breast-cancer-patients-treated-with-tamoxifen-results-from-a-population-based-study
#17
D L Hertz, K M Kidwell, S G Hilsenbeck, S Oesterreich, C K Osborne, S Philips, C Chenault, R J Hartmaier, T C Skaar, M J Sikora, J M Rae
PURPOSE: A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy...
July 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28719597/pharmacogenomics-study-of-thiazide-diuretics-and-qt-interval-in-multi-ethnic-populations-the-cohorts-for-heart-and-aging-research-in-genomic-epidemiology
#18
A A Seyerle, C M Sitlani, R Noordam, S M Gogarten, J Li, X Li, D S Evans, F Sun, M A Laaksonen, A Isaacs, K Kristiansson, H M Highland, J D Stewart, T B Harris, S Trompet, J C Bis, G M Peloso, J A Brody, L Broer, E L Busch, Q Duan, A M Stilp, C J O'Donnell, P W Macfarlane, J S Floyd, J A Kors, H J Lin, R Li-Gao, T Sofer, R Méndez-Giráldez, S R Cummings, S R Heckbert, A Hofman, I Ford, Y Li, L J Launer, K Porthan, C Newton-Cheh, M D Napier, K F Kerr, A P Reiner, K M Rice, J Roach, B M Buckley, E Z Soliman, R de Mutsert, N Sotoodehnia, A G Uitterlinden, K E North, C R Lee, V Gudnason, T Stürmer, F R Rosendaal, K D Taylor, K L Wiggins, J G Wilson, Y-DI Chen, R C Kaplan, K Wilhelmsen, L A Cupples, V Salomaa, C van Duijn, J W Jukema, Y Liu, D O Mook-Kanamori, L A Lange, R S Vasan, A V Smith, B H Stricker, C C Laurie, J I Rotter, E A Whitsel, B M Psaty, C L Avery
Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28711144/genetics-of-juvenile-idiopathic-arthritis
#19
REVIEW
Aimee O Hersh, Sampath Prahalad
Juvenile idiopathic arthritis (JIA) affects approximately 1 in 1000 US children. The cause of JIA is most likely multifactorial and due to an interplay of genetics and environmental factors. This article summarizes the known genetic risk factors for JIA that have been identified, and in some cases replicated, using a variety of methods, including genomewide association and candidate gene association studies. A brief discussion regarding pharmacogenomics and studies to data linking genetics to treatment response and outcomes is included...
August 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/28708103/pharmacogenomics-of-targeted-agents-for-personalization-of-colorectal-cancer-treatment
#20
REVIEW
Alessia Bignucolo, Elena De Mattia, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli
The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF...
July 14, 2017: International Journal of Molecular Sciences
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