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Drug Localization in Different Lung Cancer Phenotypes by MALDI Mass Spectrometry Imaging

Marko-Varga, György LU ; Fehniger, Thomas LU ; Rezeli, Melinda LU ; Döme, Balázs; Laurell, Thomas LU and Végvári, Ákos LU (2011) In Journal of Proteomics 74(7). p.982-992
Abstract
Lung cancer is a common cause of cancer mortality in the world, largely due to the risk factor of tobacco smoking. The drug therapy at the molecular level includes targeting the epidermal growth factor receptor (EGFR) tyrosine kinase activity by using inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa). The heterogeneity of disease phenotypes and the somatic mutations presented in patient populations have a great impact on the efficacy of treatments using targeted personalized medicine. In this study, we report on basic physical and chemical properties of erlotinib and gefitinib in three different lung cancer tumor phenotypes, using MALDI instrumentation in imaging mode, providing spatial localization of drugs without chemical... (More)
Lung cancer is a common cause of cancer mortality in the world, largely due to the risk factor of tobacco smoking. The drug therapy at the molecular level includes targeting the epidermal growth factor receptor (EGFR) tyrosine kinase activity by using inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa). The heterogeneity of disease phenotypes and the somatic mutations presented in patient populations have a great impact on the efficacy of treatments using targeted personalized medicine. In this study, we report on basic physical and chemical properties of erlotinib and gefitinib in three different lung cancer tumor phenotypes, using MALDI instrumentation in imaging mode, providing spatial localization of drugs without chemical labeling. Erlotinib and gefitinib were analyzed in i) planocellular lung carcinoma, ii) adenocarcinoma and iii) large cell lung carcinoma following their deposition on the tissue surfaces by piezo-dispensing, using a controlled procedure. The importance of high-resolution sampling was crucial in order to accurately localize the EGFR tyrosine-kinase inhibitors deposited in heterogeneous cancer tissue compartments. This is the first report on personalized drug characterization with localizations at a lateral resolution of 30μm, which allowed us to map these compounds at attomolar concentrations within the lung tumor tissue microenvironments. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MALDI-MS Imaging, Lung Cancer, Erlotinib, Gefitinib
in
Journal of Proteomics
volume
74
issue
7
pages
982 - 992
publisher
Elsevier
external identifiers
  • pmid:21440690
  • wos:000292440400009
  • scopus:79957632743
ISSN
1874-3919
DOI
10.1016/j.jprot.2011.03.019
project
CREATE Health
language
English
LU publication?
yes
id
9f38d253-10e0-4099-bed7-58b1a97bd53b (old id 1883395)
date added to LUP
2011-04-13 15:52:24
date last changed
2017-09-10 03:08:21
@article{9f38d253-10e0-4099-bed7-58b1a97bd53b,
  abstract     = {Lung cancer is a common cause of cancer mortality in the world, largely due to the risk factor of tobacco smoking. The drug therapy at the molecular level includes targeting the epidermal growth factor receptor (EGFR) tyrosine kinase activity by using inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa). The heterogeneity of disease phenotypes and the somatic mutations presented in patient populations have a great impact on the efficacy of treatments using targeted personalized medicine. In this study, we report on basic physical and chemical properties of erlotinib and gefitinib in three different lung cancer tumor phenotypes, using MALDI instrumentation in imaging mode, providing spatial localization of drugs without chemical labeling. Erlotinib and gefitinib were analyzed in i) planocellular lung carcinoma, ii) adenocarcinoma and iii) large cell lung carcinoma following their deposition on the tissue surfaces by piezo-dispensing, using a controlled procedure. The importance of high-resolution sampling was crucial in order to accurately localize the EGFR tyrosine-kinase inhibitors deposited in heterogeneous cancer tissue compartments. This is the first report on personalized drug characterization with localizations at a lateral resolution of 30μm, which allowed us to map these compounds at attomolar concentrations within the lung tumor tissue microenvironments.},
  author       = {Marko-Varga, György and Fehniger, Thomas and Rezeli, Melinda and Döme, Balázs and Laurell, Thomas and Végvári, Ákos},
  issn         = {1874-3919},
  keyword      = {MALDI-MS Imaging,Lung Cancer,Erlotinib,Gefitinib},
  language     = {eng},
  number       = {7},
  pages        = {982--992},
  publisher    = {Elsevier},
  series       = {Journal of Proteomics},
  title        = {Drug Localization in Different Lung Cancer Phenotypes by MALDI Mass Spectrometry Imaging},
  url          = {http://dx.doi.org/10.1016/j.jprot.2011.03.019},
  volume       = {74},
  year         = {2011},
}