Journal of Personalized Medicine

5 pages, 1239 KiB

Open AccessConference Report

ENABLE 2017, the First EUROPEAN PhD and Post-Doc Symposium. Session 3: In Vitro to In Vivo: Modeling Life in 3D

by Gianmarco Di Mauro, Ambra Dondi, Giovanni Giangreco, Alexander Hogrebe, Elja Louer, Elisa Magistrati, Meeli Mullari, Gemma Turon, Wouter Verdurmen, Helena Xicoy Cortada and Sanja Zivanovic

J. Pers. Med. 2018, 8(2), 20; https://doi.org/10.3390/jpm8020020 - 22 May 2018

Viewed by 7459

Abstract

The EUROPEAN ACADEMY FOR BIOMEDICAL SCIENCE (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European research institutes (Institute for Research in Biomedicine—IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences—RIMLS, the Netherlands; Novo Nordisk Foundation Center [...] Read more.

The EUROPEAN ACADEMY FOR BIOMEDICAL SCIENCE (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European research institutes (Institute for Research in Biomedicine—IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences—RIMLS, the Netherlands; Novo Nordisk Foundation Center for Protein Research—NNF CPR, Denmark; European School of Molecular Medicine—SEMM, Italy) and an innovative science communication agency (Scienseed). With the aim to promote biomedical science of excellence in Europe, ENABLE organizes an annual three-day international event. This gathering includes a top-level scientific symposium bringing together leading scientists, PhD students, and post-doctoral fellows; career development activities supporting the progression of young researchers and fostering discussion about opportunities beyond the bench; outreach activities stimulating the interaction between science and society. The first European PhD and Postdoc Symposium, entitled “Breaking Down Complexity: Innovative models and techniques in biomedicine”, was hosted by the vibrant city of Barcelona. The scientific program of the conference was focused on the most recent advances and applications of modern techniques and models in biomedical research and covered a wide range of topics, from synthetic biology to translational medicine. Overall, the event was a great success, with more than 200 attendees from all over Europe actively participating in the symposium by presenting their research and exchanging ideas with their peers and world-renowned scientists. Full article

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15 pages, 253 KiB

Open AccessArticle

Insurance Coverage Policies for Pharmacogenomic and Multi-Gene Testing for Cancer

by Christine Y. Lu, Stephanie Loomer, Rachel Ceccarelli, Kathleen M. Mazor, James Sabin, Ellen Wright Clayton, Geoffrey S. Ginsburg and Ann Chen Wu

J. Pers. Med. 2018, 8(2), 19; https://doi.org/10.3390/jpm8020019 - 16 May 2018

Cited by 30 | Viewed by 8924

Abstract

Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 [...] Read more.

Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 private payers for 23 biomarkers (e.g., HER2 and EGFR) and multi-gene tests. We extracted policy coverage and criteria, prior authorization requirements, and an evidence basis for coverage. We reviewed professional society guidelines and their recommendations for use of pharmacogenomic tests. Coverage for KRAS, EGFR, and BRAF tests were common across Medicare contractors and private payers, but few policies covered PML/RARA, CD25, or G6PD. Twelve payers cover at least one multi-gene test for nonsmall cell lung cancer, citing emerging clinical recommendations. Coverage policies for single and multi-gene tests for cancer treatments are relatively consistent among Medicare contractors despite the lack of national coverage determinations. In contrast, coverage for these tests varied across private payers. Patient access to tests is governed by prior authorization among eight private payers. Substantial variations in how payers address guideline-recommended pharmacogenomic tests and the common use of prior authorization underscore the need for additional studies of the effects of coverage variation on cancer care and patient outcomes. Full article

2 pages, 167 KiB

Open AccessCorrection

Correction: Antoniou, M.; et al. Fixed and Adaptive Parallel Subgroup-Specific Design for Survival Outcomes: Power and Sample Size. J. Pers. Med. 2017, 7, 19

by Miranta Antoniou, Andrea L. Jorgensen and Ruwanthi Kolamunnage-Dona

J. Pers. Med. 2018, 8(2), 18; https://doi.org/10.3390/jpm8020018 - 07 May 2018

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Abstract

The authors wish to make the following corrections to this paper [1] [...]
Full article

1 pages, 160 KiB

Open AccessCorrection

Correction: Antoniou, M.; et al. Biomarker-Guided Non-Adaptive Trial Designs in Phase II and Phase III: A Methodological Review. J. Pers. Med. 2017, 7, 1

by Miranta Antoniou, Ruwanthi Kolamunnage-Dona and Andrea L. Jorgensen

J. Pers. Med. 2018, 8(2), 17; https://doi.org/10.3390/jpm8020017 - 07 May 2018

Cited by 6 | Viewed by 5998

Abstract

The authors wish to make the following corrections to this paper [1] [...]
Full article

21 pages, 4309 KiB

Open AccessArticle

Applicability of Precision Medicine Approaches to Managing Hypertension in Rural Populations

by Jacqueline R. Halladay, Kaitlin C. Lenhart, Kimberly Robasky, Wendell Jones, Wayne F. Homan, Doyle M. Cummings, Crystal W. Cené, Alan L. Hinderliter, Cassandra L. Miller, Katrina E. Donahue, Beverly A. Garcia, Thomas C. Keyserling, Alice S. Ammerman, Cam Patterson, Darren A. DeWalt, Larry F. Johnston, Monte S. Willis and Jonathan C. Schisler

J. Pers. Med. 2018, 8(2), 16; https://doi.org/10.3390/jpm8020016 - 30 Apr 2018

Cited by 5 | Viewed by 8982

Abstract

As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: (i) to determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large studies, [...] Read more.

As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: (i) to determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large studies, are applicable to blood pressure control in subjects from a rural population; (ii) to measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and (iii) to identify other SNPs that may help understand patient-specific responses to an intervention. We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) and Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. In conclusion, the identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine. Full article

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15 pages, 1344 KiB

Open AccessFeature PaperReview

Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics

by Andrea Gaedigk, Jean C. Dinh, Hyunyoung Jeong, Bhagwat Prasad and J. Steven Leeder

J. Pers. Med. 2018, 8(2), 15; https://doi.org/10.3390/jpm8020015 - 17 Apr 2018

Cited by 100 | Viewed by 11899

Abstract

The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data [...] Read more.

The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data into a patient’s phenotype to guide drug therapy and is at the core of all CYP2D6 gene/drug pair guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The AS, however, only explains a portion of the variability observed among individuals and ethnicities. In this review, we provide an overview of sources in addition to CYP2D6 genotype that contribute to the variability in CYP2D6-mediated drug metabolism and discuss other factors, genetic and non-genetic, that likely contribute to the observed variability in CYP2D6 enzymatic activity. Full article

(This article belongs to the Special Issue Cytochrome P450 Variation in Pharmacogenomics)

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27 pages, 2759 KiB

Open AccessFeature PaperReview

Genetic Heterogeneity of SLC22 Family of Transporters in Drug Disposition

by Elisa Lozano, Oscar Briz, Rocio I. R. Macias, Maria A. Serrano, Jose J. G. Marin and Elisa Herraez

J. Pers. Med. 2018, 8(2), 14; https://doi.org/10.3390/jpm8020014 - 16 Apr 2018

Cited by 28 | Viewed by 8918

Abstract

An important aspect of modern medicine is its orientation to achieve more personalized pharmacological treatments. In this context, transporters involved in drug disposition have gained well-justified attention. Owing to its broad spectrum of substrate specificity, including endogenous compounds and xenobiotics, and its strategical [...] Read more.

An important aspect of modern medicine is its orientation to achieve more personalized pharmacological treatments. In this context, transporters involved in drug disposition have gained well-justified attention. Owing to its broad spectrum of substrate specificity, including endogenous compounds and xenobiotics, and its strategical expression in organs accounting for drug disposition, such as intestine, liver and kidney, the SLC22 family of transporters plays an important role in physiology, pharmacology and toxicology. Among these carriers are plasma membrane transporters for organic cations (OCTs) and anions (OATs) with a marked overlap in substrate specificity. These two major clades of SLC22 proteins share a similar membrane topology but differ in their degree of genetic variability. Members of the OCT subfamily are highly polymorphic, whereas OATs have a lower number of genetic variants. Regarding drug disposition, changes in the activity of these variants affect intestinal absorption and target tissue uptake, but more frequently they modify plasma levels due to enhanced or reduced clearance by the liver and secretion by the kidney. The consequences of these changes in transport-associated function markedly affect the effectiveness and toxicity of the treatment in patients carrying the mutation. In solid tumors, changes in the expression of these transporters and the existence of genetic variants substantially determine the response to anticancer drugs. Moreover, chemoresistance usually evolves in response to pharmacological and radiological treatment. Future personalized medicine will require monitoring these changes in a dynamic way to adapt the treatment to the weaknesses shown by each tumor at each stage in each patient. Full article

(This article belongs to the Special Issue Personalized Medicine Based on Drug Transporter Genetic Heterogeneity)

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22 pages, 2535 KiB

Open AccessArticle

Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly Mutated Wnt/β-Catenin Pathway Associated with Oncogenic EGFR Mutations

by Jingrui Jiang, Alexei Protopopov, Ruobai Sun, Stephen Lyle and Meaghan Russell

J. Pers. Med. 2018, 8(2), 13; https://doi.org/10.3390/jpm8020013 - 09 Apr 2018

Cited by 6 | Viewed by 8556

Abstract

Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to [...] Read more.

Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS)-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples. We found that activating EGFR mutations were predominantly detected in lung cancer, particularly in non-small cell lung cancer (NSCLC). The mutational landscape of EGFR-driven tumors covered most key signaling pathways and biological processes. Strikingly, the Wnt/β-catenin pathway was highly mutated (48 variants detected in 46% of the EGFR-driven tumors), and its variant number topped that in the TP53/apoptosis and PI3K-AKT-mTOR pathways. Furthermore, an analysis of mutation distribution revealed a differential association pattern of gene mutations between EGFR exon 19del and EGFR L858R. Our results confirm the aggressive nature of the oncogenic EGFR-driven tumors and reassure that a combinational strategy should have advantages over an EGFR-targeted monotherapy and holds great promise for overcoming drug resistance. Full article

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J. Pers. Med., Volume 8, Issue 2 (June 2018) – 8 articles

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