Signal transduction therapeutics is now the dominant theme of drug discover
y, and its most immediate impact will be in cancer therapeutics, Blood cell
proliferation, differentiation, and activation are controlled by cytokines
, whose receptors contain tyrosine kinase catalytic domains or recruit cyto
solic tyrosine kinases, Among the most important cytosolic protein tyrosine
kinases are the Src and Jak families, Receptor or cytosolic protein tyrosi
ne kinases activate a similar set of intracellular signaling molecules. In
blood cells, excessive tyrosine kinase activity is associated with either c
ancer or autoreactive diseases. Therefore, tyrosine kinases and their subst
rates serve as excellent candidates for drug intervention. Herceptin has be
en approved for use in breast cancer, Other agents, such as SU101 and CGP 5
7418B, are well into phase I-III trials. Newer, more selective tyrosine kin
ase inhibitors are being evaluated for future use in the treatment of hemat
ologic and solid tumors as well as a wide range of inflammatory off autoimm
une diseases.