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Pharmacogenetics and Personalized Medicine 2016

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 December 2016) | Viewed by 65991

Special Issue Editors

Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio, n 48, IT-40126, Bologna, Italy
Interests: pharmacogenetic studies; biomarkers of effect and susceptibility in populations exposed to pollutants; epidemiological studies in populations exposed to ionizing radiation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The accomplishment of the Human Genome Project, followed by the availability of high-throughput technologies, has led to a dramatic change in biomedical research. In particular, the emergency of new tools for genome analysis has contributed to our knowledge of the molecular mechanisms defining pathways that might reasonably influence therapy and response. This knowledge has paved the way to the development of personalized medicine, which aims to determine unique individuals’ molecular characteristics and select better treatments, and reduce possible drug adverse reactions. Despite personalized medicine being an attractive strategy in disease treatment (and there is a great interest in the development of powerful approaches to be incorporated into clinical practice), persistent gaps do exist between published research and clinical application.

Topics of the Special Issue include, but are not limited to:

  • Genetic variability on drug toxicity and efficacy
  • Genomic and proteomic profiling
  • miRNA profiles to predict prognosis and outcome
  • Multi-omics approaches to the study of treatment response
  • The use of genomics in model organisms of treatment response
  • Epigenetic changes as determinants of drug response/resistance
  • Novel genomic targets for drug development
  • Stem cell as new therapeutic option for untreatable disease
  • Pharmacometabonomics a promising tool for monitoring therapy effectiveness on the basis of mathematical models of pre-dose metabolite profiles

Prof. Dr. Sabrina Angelini 
Dr. Gloria Ravegnini 
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pharmacogenetics
  • pharmacogenomics
  • pharmacometabonomics
  • genetic variability
  • miRNA
  • Epigenetics

Related Special Issue

Published Papers (7 papers)

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Research

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523 KiB  
Article
OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings
by Aline Hajj, Lucine Halepian, Nada El Osta, Georges Chahine, Joseph Kattan and Lydia Rabbaa Khabbaz
Int. J. Mol. Sci. 2017, 18(4), 669; https://doi.org/10.3390/ijms18040669 - 27 Mar 2017
Cited by 26 | Viewed by 6246
Abstract
Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL). We conducted this study to evaluate the added value of determining some genetic and [...] Read more.
Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL). We conducted this study to evaluate the added value of determining some genetic and non-genetic factors to optimize cancer pain treatment. Eighty-nine patients were included in the study for the evaluation of palliative cancer pain management. The regression analysis showed that age, OPRM1 single nucleotide polymorphism (SNP), as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h (given by infusion pump; p = 0.043, 0.029, and <0.001, respectively). The mean doses of morphine decreased with age but increased with the duration of morphine treatment. In addition, patients with AG genotype c.118A>G OPRM1 needed a higher dose of morphine than AA patients. Moreover, metastases, OPRM1 SNP, age, and gender were significantly associated with the QOL in our population. In particular, AA patients for OPRM1 SNP had significantly lower cognitive function than AG patients, a result not previously reported in the literature. These findings could help increase the effectiveness of morphine treatment and enhance the QOL of patients in regards to personalized medicine. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
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657 KiB  
Article
Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients
by Eva Dreussi, Erika Cecchin, Jerry Polesel, Vincenzo Canzonieri, Marco Agostini, Caterina Boso, Claudio Belluco, Angela Buonadonna, Sara Lonardi, Francesca Bergamo, Sara Gagno, Elena De Mattia, Salvatore Pucciarelli, Antonino De Paoli and Giuseppe Toffoli
Int. J. Mol. Sci. 2016, 17(9), 1482; https://doi.org/10.3390/ijms17091482 - 05 Sep 2016
Cited by 10 | Viewed by 5260
Abstract
Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this [...] Read more.
Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
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Review

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1319 KiB  
Review
State of Art of Cancer Pharmacogenomics in Latin American Populations
by Andrés López-Cortés, Santiago Guerrero, María Ana Redal, Angel Tito Alvarado and Luis Abel Quiñones
Int. J. Mol. Sci. 2017, 18(6), 639; https://doi.org/10.3390/ijms18060639 - 23 May 2017
Cited by 21 | Viewed by 8089
Abstract
Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the [...] Read more.
Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations. In this review, we present the current status of research on somatic and germline alterations in Latin America compared to those found in Caucasian and Asian populations. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
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6005 KiB  
Review
Parkinson’s Disease: From Pathogenesis to Pharmacogenomics
by Ramón Cacabelos
Int. J. Mol. Sci. 2017, 18(3), 551; https://doi.org/10.3390/ijms18030551 - 04 Mar 2017
Cited by 354 | Viewed by 26078
Abstract
Parkinson’s disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. [...] Read more.
Parkinson’s disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson’s disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson’s disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin–proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol-O-methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the “wearing-off phenomenon”, with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to enhancing dopaminergic neurotransmission. Since biochemical changes and therapeutic outcomes are highly dependent upon the genomic profiles of PD patients, personalized treatments should rely on pharmacogenetic procedures to optimize therapeutics. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
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4326 KiB  
Review
Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations
by Savita Nandal and Tal Burt
Int. J. Mol. Sci. 2017, 18(2), 448; https://doi.org/10.3390/ijms18020448 - 19 Feb 2017
Cited by 16 | Viewed by 5907
Abstract
Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in [...] Read more.
Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
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730 KiB  
Review
Pharmacogenetic Foundations of Therapeutic Efficacy and Adverse Events of Statins
by Elena Arrigoni, Marzia Del Re, Leonardo Fidilio, Stefano Fogli, Romano Danesi and Antonello Di Paolo
Int. J. Mol. Sci. 2017, 18(1), 104; https://doi.org/10.3390/ijms18010104 - 06 Jan 2017
Cited by 30 | Viewed by 7177
Abstract
Background: In the era of precision medicine, more attention is paid to the search for predictive markers of treatment efficacy and tolerability. Statins are one of the classes of drugs that could benefit from this approach because of their wide use and their [...] Read more.
Background: In the era of precision medicine, more attention is paid to the search for predictive markers of treatment efficacy and tolerability. Statins are one of the classes of drugs that could benefit from this approach because of their wide use and their incidence of adverse events. Methods: Literature from PubMed databases and bibliography from retrieved publications have been analyzed according to terms such as statins, pharmacogenetics, epigenetics, toxicity and drug–drug interaction, among others. The search was performed until 1 October 2016 for articles published in English language. Results: Several technical and methodological approaches have been adopted, including candidate gene and next generation sequencing (NGS) analyses, the latter being more robust and reliable. Among genes identified as possible predictive factors associated with statins toxicity, cytochrome P450 isoforms, transmembrane transporters and mitochondrial enzymes are the best characterized. Finally, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) transporter seems to be the best target for future studies. Moreover, drug–drug interactions need to be considered for the best approach to personalized treatment. Conclusions: Pharmacogenetics of statins includes several possible genes and their polymorphisms, but muscular toxicities seem better related to SLCO1B1 variant alleles. Their analysis in the general population of patients taking statins could improve treatment adherence and efficacy; however, the cost–efficacy ratio should be carefully evaluated. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
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700 KiB  
Review
The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors—Is Pharmacogenetics the Key?
by Aizati N. A. Daud, Jorieke E. H. Bergman, Wilhelmina S. Kerstjens-Frederikse, Henk Groen and Bob Wilffert
Int. J. Mol. Sci. 2016, 17(8), 1333; https://doi.org/10.3390/ijms17081333 - 13 Aug 2016
Cited by 11 | Viewed by 6499
Abstract
Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these [...] Read more.
Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these drugs. However, subsequent studies have reported conflicting results on the association between CHA and SRI use during pregnancy. These discrepancies in the risk estimates can potentially be explained by genetic differences among exposed individuals. In this review, we explore the potential pharmacogenetic predictors involved in the pharmacokinetics and mechanism of action of SRIs, and their relation to the risk of CHA. In general, the risk is dependent on the maternal concentration of SRIs and the foetal serotonin level/effect, which can be modulated by the alteration in the expression and/or function of the metabolic enzymes, transporter proteins and serotonin receptors involved in the serotonin signalling of the foetal heart development. Pharmacogenetics might be the key to understanding why some children exposed to SRIs develop a congenital heart anomaly and others do not. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
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