The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a
cancer patient with inhibitors of EGFR
kinase, PDGFR
kinase, or FGFR
kinase. Based on the surprising discovery that tumors cells after having undergone an EMT, while being mesenchymal-like, still express characteristics of both epithelial and mesenchymal cells, and that such cells have altered sensitivity to inhibition by
receptor protein-
tyrosine kinase inhibitors, in that they have become relatively insensitive to EGFR kinase inhibitors, but have frequently acquired sensitivity to inhibitors of other
receptor protein-
tyrosine kinases such as PDGFR or FGFR, methods have been devised for determining levels of specific epithelial and mesenchymal biomarkers that identify such ā
hybridā
tumor cells (e.g. determination of co-expression of
vimentin and epithelial keratins), and thus predict the tumor's likely sensitivity to inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Improved methods for treating
cancer patients with EGFR, PDGFR or FGFR kinase inhibitors that incorporate such methodology are also provided.