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A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging

Sugihara, Yutaka LU ; Végvári, Ákos LU ; Welinder, Charlotte LU ; Jönsson, Göran B LU ; Ingvar, Christian LU ; Lundgren, Lotta LU ; Olsson, Håkan LU ; Breslin, Thomas LU ; Wieslander, Elisabet LU and Laurell, Thomas LU , et al. (2014) In Proteomics 14(17-18). p.1963-1970
Abstract
Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BRAF mutated protein, has shown significant efficacy in slowing disease progression. In this paper we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of personalized medicine drugs within tumor compartments. In this study, we have introduced matrix-assisted laser desorption/ionization mass... (More)
Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BRAF mutated protein, has shown significant efficacy in slowing disease progression. In this paper we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of personalized medicine drugs within tumor compartments. In this study, we have introduced matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MSI was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using mass spectrometry fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment. (Less)
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Contribution to journal
publication status
published
subject
keywords
Clinical studies, Genes, Malignant melanoma, Personalized medicine, Protein sequencing, Proteomics, Mass spectrometry imaging
in
Proteomics
volume
14
issue
17-18
pages
1963 - 1970
publisher
John Wiley & Sons
external identifiers
  • wos:000342912600003
  • pmid:25044963
  • scopus:84908608666
ISSN
1615-9861
DOI
10.1002/pmic.201300476
language
English
LU publication?
yes
id
1ccef2f8-3827-47d5-8c53-0a5ce252e901 (old id 4247034)
date added to LUP
2014-08-21 14:14:29
date last changed
2017-05-21 03:18:24
@article{1ccef2f8-3827-47d5-8c53-0a5ce252e901,
  abstract     = {Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BRAF mutated protein, has shown significant efficacy in slowing disease progression. In this paper we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of personalized medicine drugs within tumor compartments. In this study, we have introduced matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MSI was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using mass spectrometry fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment.},
  author       = {Sugihara, Yutaka and Végvári, Ákos and Welinder, Charlotte and Jönsson, Göran B and Ingvar, Christian and Lundgren, Lotta and Olsson, Håkan and Breslin, Thomas and Wieslander, Elisabet and Laurell, Thomas and Rezeli, Melinda and Jansson, Bo and Fehniger, Thomas and Baldetorp, Bo and Marko-Varga, György},
  issn         = {1615-9861},
  keyword      = {Clinical studies,Genes,Malignant melanoma,Personalized medicine,Protein sequencing,Proteomics,Mass spectrometry imaging},
  language     = {eng},
  number       = {17-18},
  pages        = {1963--1970},
  publisher    = {John Wiley & Sons},
  series       = {Proteomics},
  title        = {A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging},
  url          = {http://dx.doi.org/10.1002/pmic.201300476},
  volume       = {14},
  year         = {2014},
}