Raman Microspectroscopic Evidence for the Metabolism of a Tyrosine Kinase Inhibitor,Neratinib, in Cancer Cells |
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| Authors: | Karim Aljakouch Tatjana Lechtonen Dr. Hesham K. Yosef Mohamad K. Hammoud Wissam Alsaidi Dr. Carsten Kötting Dr. Carolin Mügge Prof. Dr. Robert Kourist Dr. Samir F. El‐Mashtoly Prof. Dr. Klaus Gerwert |
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| Affiliation: | 1. http://www.bph.rub.de/ 0000-0002-8330-512X Biophysics Department, Ruhr-University Bochum, Germany;2. Biophysics Department, Ruhr-University Bochum, Germany;3. Junior Research Group for Microbial Biotechnology, Ruhr-University Bochum, Germany;4. Institute of Molecular Biotechnology, Graz University of Technology, Austria |
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| Abstract: | Tyrosine kinase receptors are one of the main targets in cancer therapy. They play an essential role in the modulation of growth factor signaling and thereby inducing cell proliferation and growth. Tyrosine kinase inhibitors such as neratinib bind to EGFR and HER2 receptors and exhibit antitumor activity. However, little is known about their detailed cellular uptake and metabolism. Here, we report for the first time the intracellular spatial distribution and metabolism of neratinib in different cancer cells using label‐free Raman imaging. Two new neratinib metabolites were detected and fluorescence imaging of the same cells indicate that neratinib accumulates in lysosomes. The results also suggest that both EGFR and HER2 follow the classical endosome lysosomal pathway for degradation. A combination of Raman microscopy, DFT calculations, and LC‐MS was used to identify the chemical structure of neratinib metabolites. These results show the potential of Raman microscopy to study drug pharmacokinetics. |
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| Keywords: | cancer label-free imaging metabolism Raman spectroscopy tyrosine kinase inhibitors |
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