Sh2 Domain Profiling to Characterize Tyrosine Phosphorylation Signaling in Cancer

A phosphoproteomic method termed SH2 profiling to characterize phosphotyrosine (pTyr) signaling in lung cancer. This method provides quantitative values for the phosphorylated binding sites for Src Homology 2 (SH2) domains, which the cell uses to relay signals from tyrosine kinases. Lung cancer cell lines with known mutational status of the epidermal growth factor receptor (EGFR) and Ras were profiled. Changes in SH2 domain binding were characterized in response to the EGFR inhibitor erlotinib, and the SRC/multi-kinase inhibitor dasatinib. Cell lines grouped based on SH2 binding patterns. Clusters correlated with EGFR mutation status or MET activation. Binding of specific SH2 domains correlated with EGFR mutation and erlotinib sensitivity. SH2 domain profiling identifies subsets of lung cancer cells with distinct patterns of pTyr signaling and provides a powerful molecular diagnostic tool for classification and biomarker identification. This analysis has therapeutic importance for personalized use of tyrosine kinase inhibitors in cancer.

Attached files:


Patents:
WO 2,011,034,919

Inventor(s): HAURA ERIC B [US]; ESCHRICH STEVEN A [US]; MAYER BRUCE J [US]; MACHIDA KAZUYA [US]

Type of Offer: Licensing



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