The present invention describes polynucleotides that have been discovered to correlate to the relative intrinsic sensitivity or resistance of cells, e.g.,
lung cell lines, to treatment with compounds that interact with and modulate, e.g., inhibit,
protein tyrosine kinases, such as, for example, members of the
Src family of
tyrosine kinases, e.g., Src, Fgr, Fyn, Yes, Blk, Hck, Lck and Lyn, as well as other
protein tyrosine kinases, including, Bcr-
abl, Jak, PDGFR, c-kit and Ephr. These polynucleotides have been shown, through a weighted voting
cross validation program, to have utility in predicting the resistance and sensitivity of
lung cell lines to the compounds. The expression level of some polynucleotides is regulated by treatment with a particular
protein tyrosine kinase inhibitor compound, thus indicating that these polynucleotides are involved in the protein
tyrosine kinase signal transduction pathway, e.g., Src
tyrosine kinase. Such polynucleotides, whose expression levels correlate highly with
drug sensitivity or resistance and which are modulated by treatment with the compounds, comprise
polynucleotide predictor or marker sets useful in methods of predicting
drug response, and as prognostic or diagnostic indicators in
disease management, particularly in those
disease areas, e.g.,
lung cancer, in which signaling through the protein tyrosine
kinase pathway, such as the Src tyrosine
kinase pathway, is involved with the
disease process.