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Pharmacogenetics and Personalized Medicine

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Book cover Drug Design: Principles and Applications

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.

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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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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, Pisa, 56126, Italy

    Antonello Di Paolo M.D., Ph.D., Elena Arrigoni, Sara Galimberti & Romano Danesi

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  1. Antonello Di Paolo M.D., Ph.D.
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  2. Elena Arrigoni
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  3. Sara Galimberti
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  4. Romano Danesi
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Correspondence to Antonello Di Paolo M.D., Ph.D. .

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  1. School of Biotechnology, Jawaharlal Nehru University, New Delhi, India

    Abhinav Grover

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Di Paolo, A., Arrigoni, E., Galimberti, S., Danesi, R. (2017). Pharmacogenetics and Personalized Medicine. In: Grover, A. (eds) Drug Design: Principles and Applications. Springer, Singapore. https://doi.org/10.1007/978-981-10-5187-6_10

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