Impact of single nucleotide polymorphisms on the efficacy and toxicity of egfr tyrosine kinase inhibitors in advanced non-small cell lung cancer patients.

Cristina Perez-Ramirez, Marisa Cañadas-Garre, Miguel Angel Molina, Jose Cabeza Barrera, Maria Jose Faus Dader

Research output: Contribution to journalReview article

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Abstract

EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the treatment of choice for advanced-stage (IIIB-IV) NSCLC patients with mutations in EGFR. However, EGFR-TKIs clinical outcomes vary from person to person and these inter-individual differences may be due to genetic factors such as single nucleotide polymorphisms (SNPs). SNPs in genes involved in in EGFR-TKIs pharmacodynamics, metabolism and mechanism of action have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with EGFR-TKIs.
Here we review the influence of gene polymorphisms in the EGFR pathway on clinical outcome and toxicity to EGFR-TKIs in advanced NSCLC patients. The EGFR-216 polymorphism has reported a strong association between response and/or survival to EGFR-TKIs in Caucasian population. Similarly, the effect of EGFR-CA repeats polymorphisms on survival of advanced NSCLC patients treated with EGFR-TKIs have been confirmed both in Caucasian and Asian population. The influence on toxicity of the -216, -191, CA repeats, Arg497Lys and Asp994Asp polymorphisms in EGFR have also been confirmed. Polymorphisms in AKT (rs1130214 and rs1130233) and SMAD3 (rs6494633, rs11071938 and rs11632964) have been associated with survival in advanced NSCLC patients treated with EGFR-TKIs. However, data come from a limited number of studies and need to be confirmed.
Finally, polymorphisms in genes coding proteins of the membrane transporters and cytochrome P450 enzymes have been less extensively investigated. There are few studies with small samples, which complicated the generalization of their role in EGFR-TKIs treatment.
Original languageEnglish
JournalMutation research-Reviews in mutation research
Early online date09 Apr 2019
DOIs
Publication statusEarly online date - 09 Apr 2019

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Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Single Nucleotide Polymorphism
Survival
Cytochrome P-450 Enzyme System
Critical Pathways
Membrane Transport Proteins
Individuality
Population
Genes
Mutation
Therapeutics

Cite this

@article{4b5f4a2e85104b1c86a72fd634db765c,
title = "Impact of single nucleotide polymorphisms on the efficacy and toxicity of egfr tyrosine kinase inhibitors in advanced non-small cell lung cancer patients.",
abstract = "EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the treatment of choice for advanced-stage (IIIB-IV) NSCLC patients with mutations in EGFR. However, EGFR-TKIs clinical outcomes vary from person to person and these inter-individual differences may be due to genetic factors such as single nucleotide polymorphisms (SNPs). SNPs in genes involved in in EGFR-TKIs pharmacodynamics, metabolism and mechanism of action have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with EGFR-TKIs.Here we review the influence of gene polymorphisms in the EGFR pathway on clinical outcome and toxicity to EGFR-TKIs in advanced NSCLC patients. The EGFR-216 polymorphism has reported a strong association between response and/or survival to EGFR-TKIs in Caucasian population. Similarly, the effect of EGFR-CA repeats polymorphisms on survival of advanced NSCLC patients treated with EGFR-TKIs have been confirmed both in Caucasian and Asian population. The influence on toxicity of the -216, -191, CA repeats, Arg497Lys and Asp994Asp polymorphisms in EGFR have also been confirmed. Polymorphisms in AKT (rs1130214 and rs1130233) and SMAD3 (rs6494633, rs11071938 and rs11632964) have been associated with survival in advanced NSCLC patients treated with EGFR-TKIs. However, data come from a limited number of studies and need to be confirmed.Finally, polymorphisms in genes coding proteins of the membrane transporters and cytochrome P450 enzymes have been less extensively investigated. There are few studies with small samples, which complicated the generalization of their role in EGFR-TKIs treatment.",
author = "Cristina Perez-Ramirez and Marisa Ca{\~n}adas-Garre and Molina, {Miguel Angel} and {Cabeza Barrera}, Jose and {Faus Dader}, {Maria Jose}",
year = "2019",
month = "4",
day = "9",
doi = "10.1016/j.mrrev.2019.04.001",
language = "English",
journal = "Mutation Research - Reviews",
issn = "1383-5742",
publisher = "Elsevier",

}

Impact of single nucleotide polymorphisms on the efficacy and toxicity of egfr tyrosine kinase inhibitors in advanced non-small cell lung cancer patients. / Perez-Ramirez, Cristina; Cañadas-Garre, Marisa; Molina, Miguel Angel; Cabeza Barrera, Jose; Faus Dader, Maria Jose.

In: Mutation research-Reviews in mutation research, 09.04.2019.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Impact of single nucleotide polymorphisms on the efficacy and toxicity of egfr tyrosine kinase inhibitors in advanced non-small cell lung cancer patients.

AU - Perez-Ramirez, Cristina

AU - Cañadas-Garre, Marisa

AU - Molina, Miguel Angel

AU - Cabeza Barrera, Jose

AU - Faus Dader, Maria Jose

PY - 2019/4/9

Y1 - 2019/4/9

N2 - EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the treatment of choice for advanced-stage (IIIB-IV) NSCLC patients with mutations in EGFR. However, EGFR-TKIs clinical outcomes vary from person to person and these inter-individual differences may be due to genetic factors such as single nucleotide polymorphisms (SNPs). SNPs in genes involved in in EGFR-TKIs pharmacodynamics, metabolism and mechanism of action have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with EGFR-TKIs.Here we review the influence of gene polymorphisms in the EGFR pathway on clinical outcome and toxicity to EGFR-TKIs in advanced NSCLC patients. The EGFR-216 polymorphism has reported a strong association between response and/or survival to EGFR-TKIs in Caucasian population. Similarly, the effect of EGFR-CA repeats polymorphisms on survival of advanced NSCLC patients treated with EGFR-TKIs have been confirmed both in Caucasian and Asian population. The influence on toxicity of the -216, -191, CA repeats, Arg497Lys and Asp994Asp polymorphisms in EGFR have also been confirmed. Polymorphisms in AKT (rs1130214 and rs1130233) and SMAD3 (rs6494633, rs11071938 and rs11632964) have been associated with survival in advanced NSCLC patients treated with EGFR-TKIs. However, data come from a limited number of studies and need to be confirmed.Finally, polymorphisms in genes coding proteins of the membrane transporters and cytochrome P450 enzymes have been less extensively investigated. There are few studies with small samples, which complicated the generalization of their role in EGFR-TKIs treatment.

AB - EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the treatment of choice for advanced-stage (IIIB-IV) NSCLC patients with mutations in EGFR. However, EGFR-TKIs clinical outcomes vary from person to person and these inter-individual differences may be due to genetic factors such as single nucleotide polymorphisms (SNPs). SNPs in genes involved in in EGFR-TKIs pharmacodynamics, metabolism and mechanism of action have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with EGFR-TKIs.Here we review the influence of gene polymorphisms in the EGFR pathway on clinical outcome and toxicity to EGFR-TKIs in advanced NSCLC patients. The EGFR-216 polymorphism has reported a strong association between response and/or survival to EGFR-TKIs in Caucasian population. Similarly, the effect of EGFR-CA repeats polymorphisms on survival of advanced NSCLC patients treated with EGFR-TKIs have been confirmed both in Caucasian and Asian population. The influence on toxicity of the -216, -191, CA repeats, Arg497Lys and Asp994Asp polymorphisms in EGFR have also been confirmed. Polymorphisms in AKT (rs1130214 and rs1130233) and SMAD3 (rs6494633, rs11071938 and rs11632964) have been associated with survival in advanced NSCLC patients treated with EGFR-TKIs. However, data come from a limited number of studies and need to be confirmed.Finally, polymorphisms in genes coding proteins of the membrane transporters and cytochrome P450 enzymes have been less extensively investigated. There are few studies with small samples, which complicated the generalization of their role in EGFR-TKIs treatment.

U2 - 10.1016/j.mrrev.2019.04.001

DO - 10.1016/j.mrrev.2019.04.001

M3 - Review article

JO - Mutation Research - Reviews

JF - Mutation Research - Reviews

SN - 1383-5742

ER -