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Pharmacogenetics and Personalized Medicine

  • Antonello Di PaoloEmail author
  • Elena Arrigoni
  • Sara Galimberti
  • Romano Danesi
Chapter

Abstract

Recent advances in the comprehension of pathogenic mechanisms of human diseases have brought the researchers to the discovery of putative pharmacological targets and the subsequent development of the so-called targeted drugs. In order to maximize their efficacy, as well as that of the other drugs, it is imperative to identify those patients that are more prone to experience a therapeutic benefit. In the pharmacogenetic area, several strategies may be pursued to assay biomarkers. The quantitation of gene expression, the identification of changes in gene and chromosomal sequences, and the evaluation of epigenetic factors may contribute to anticipate drug efficacy and tolerability. At those levels, the number of candidate genes that may be investigated is highly variable, up to the evaluation of the whole human genome. Despite the increasing complexity of pharmacogenetic analyses and their interpretation, some relationships between genetic biomarkers and treatment outcomes may be characterized by suboptimal values of sensitivity and specificity. For that reason, the validation of the biomarkers and their transfer into the clinics are the major challenges.

Keywords

Pharmacogenetics Gene expression Polymorphisms Mutations Gene amplification Deletion Biomarkers Next-generation sequencing Genome-wide association studies Microarray Study design 

Abbreviations

3′-UTR

3′-Untranslated region

5-FU

5-Fluoruracil

ABCB1

ATP-binding cassette transporter family member B1

AIFA

Italian Medicine Agency

AML

Acute myeloid leukemia

BCR-Abl

Breakpoint cluster region-Abelson

CML

Chronic myeloid leukemia

CRC

Colorectal cancer

CYP2D6

Cytochrome P450 isoform 2D6

CYP3A4

Cytochrome P450 isoform 3A4

CYP450

Cytochrome P450

ddPCR

Digital droplet PCR

DNMT

DNA methyl transferase

dpydDPD

Dihydropyrimidine dehydrogenase

EGFR

Epithelial growth factor receptor

ELN

European Leukemia Network

FDA

Food and Drug Administration

HAT

Histone acetyltransferase

HDAC

Histone deacetyltransferase

HMGCoA

Hydroxymethyl-glutaryl coenzyme A

hOCT1

Human organic cation transporter family member 1

lncRNA

Long-noncoding RNA

miRNA

microRNA

NAT

N-acetyl transferase

ncRNA

Noncoding RNA

NGS

Next-generation sequencing

NSAID

Nonsteroidal anti-inflammatory drug

NSCLC

Non-small-cell lung cancer

OS

Overall survival

PCR

Polymerase chain reaction

PFS

Progression-free survival

RR

Response rate

SLCO1B1

Solute carrier organic anion transporter family member 1B1

SLCO1B3

Solute carrier organic anion transporter family member 1B3

SNP

Single-nucleotide polymorphism

TYMS

Thymidylate synthase

WGAS

Genome-wide association study

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Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Antonello Di Paolo
    • 1
    Email author
  • Elena Arrigoni
    • 1
  • Sara Galimberti
    • 1
  • Romano Danesi
    • 1
  1. 1.Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly

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