Global quantitative phosphoproteome analyses provide detailed insights into the cellular mode of action of targeted cancer drugs. Furthermore, regulated protein phosphorylations may be used as biomarkers to predict the outcomes of drug treatment. Proteome labeling methods such as stable isotope labeling by amino acids in cell culture (SILAC) are employed for quantitative mass spectrometry analysis of cell line and tissue samples. Combining these methods with state-of-the-art bioinformatics help reveal a compound's impact on signal transduction pathways. KINAXO has applied this approach to sorafenib (NexavarTM, Bayer Healthcare), a targeted drug approved for the treatment of kidney and liver cancer. Our findings suggest a previously unpublished mode of action for sorafenib through inhibition of the mTOR pathway in prostate cancer cells (PC-3). Recently, the collaboration with Bayer has been expanded to biomarker discovery in acute myeloid leukemia (AML).
Flow Chemistry