Back to Search Start Over

Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity

Authors :
Yitian Zhou
Magnus Ingelman-Sundberg
Volker M. Lauschke
Source :
Pharmacology & Therapeutics
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

Individuals differ substantially in their response to pharmacological treatment. Personalized medicine aspires to embrace these inter-individual differences and customize therapy by taking a wealth of patient-specific data into account. Pharmacogenomic constitutes a cornerstone of personalized medicine that provides therapeutic guidance based on the genomic profile of a given patient. Pharmacogenomics already has applications in the clinics, particularly in oncology, whereas future development in this area is needed in order to establish pharmacogenomic biomarkers as useful clinical tools. In this review we present an updated overview of current and emerging pharmacogenomic biomarkers in different therapeutic areas and critically discuss their potential to transform clinical care. Furthermore, we discuss opportunities of technological, methodological and institutional advances to improve biomarker discovery. We also summarize recent progress in our understanding of epigenetic effects on drug disposition and response, including a discussion of the only few pharmacogenomic biomarkers implemented into routine care. We anticipate, in part due to exciting rapid developments in Next Generation Sequencing technologies, machine learning methods and national biobanks, that the field will make great advances in the upcoming years towards unlocking the full potential of genomic data.

Subjects

Subjects :
0301 basic medicine
SJS, Stevens-Johnson syndrome
DNMTs, DNA methyltransferases
PTMs, Posttranslational modifications
Epigenesis, Genetic
TAB-Seq, TET-assisted bisulfite sequencing
MAF, Minor allele frequencies
SCAR, Severe cutaneous adverse reaction
0302 clinical medicine
ChIP, Chromatin immunoprecipitation
CFTR, Cystic fibrosis transmembrane conductance regulator
Medicine
eQTL, Quantitative trait locus
Pharmacology (medical)
Biomarker discovery
PRC2, Polycomb repressive complex 2
5hmC, 5-hydroxymethylcytosine
UM, Ultrarapid metabolism
education.field_of_study
MS, Multiple sclerosis
High-Throughput Nucleotide Sequencing
TEN, Toxic epidermal necrolysis
Biobank
CPIC, Clinical Pharmacogenetics Implementation Consortium
3. Good health
PM, Poor metabolism
030220 oncology & carcinogenesis
GST, Glutathione-S-transferase
SNVs, Single nucleotide variations
DIHS, Drug-induced hypersensitivity syndrome
Drug-Related Side Effects and Adverse Reactions
5fC, 5- Formylcytosine
Population
MEDLINE
5caC, 5- Carboxylcytosine
DPWG, Dutch Pharmacogenetics Working Group
Article
03 medical and health sciences
HDACs, Histone deacetylases
RA, Retinoic acid
ABC-HSS, Abacavir hypersensitivity syndrome
Animals
Humans
Pharmacokinetics
MPE, Maculopapular exanthema
education
Pharmacology
oxBS-seq, Oxidative bisulfite sequencing
business.industry
DILI, Drug-induced liver injury
CNVs, Copy number variations
DRESS, Drug rash with eosinophilia and systemic symptoms
Data science
CAT, Catalase
GPCR, G-protein coupled receptor
030104 developmental biology
ALL, Acute lymphoblastic leukemia
Biological Variation, Population
Pharmacogenetics
Pharmacogenomics
Genomic Profile
Personalized medicine
DHR, Drug hypersensitivity reactions
business
Biomarkers

Details

ISSN :
01637258
Volume :
197
Database :
OpenAIRE
Journal :
Pharmacology & Therapeutics
Accession number :
edsair.doi.dedup.....1c77b497b32c4399ec51c1cb33968c9c