Journal
PROTEOMICS
Volume 14, Issue 17-18, Pages 1963-1970Publisher
WILEY
DOI: 10.1002/pmic.201300476
Keywords
Biomedicine; Clinical studies; Malignant melanoma; Personalized medicine; Protein sequencing; Mass spectrometry imaging
Funding
- Mrs. Berta Kamprad Foundation
- Swedish Academy of Pharmaceutical Sciences
- Swedish Research Council
- Swedish Foundation for Strategic Research
- Vinnova
- Ingabritt & Arne Lundbergs forskningsstiftelse
- Crafoord Foundation
- Innovative Support for CREATE Health [2011-039226]
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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 has been highly effective for certain subsets of MM patients. Vemurafenib, a protein kinase inhibitor 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 PM drugs within tumor compartments. In this study, we have introduced MALDI-MS imaging 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-MS imaging 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 MS 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.
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