Implications for Src kinases in hematopoiesis: signal transduction therapeutics

Signal transduction therapeutics is now the dominant theme of drug discovery, 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 cytosolic tyrosine kinases. Among the most important cytosolic protein tyrosine kinases are the Src and Jak families. Receptor or cytosolic protein tyrosine kinases activate a similar set of intracellular signaling molecules. In blood cells, excessive tyrosine kinase activity is associated with either cancer or autoreactive diseases. Therefore, tyrosine kinases and their substrates serve as excellent candidates for drug intervention. Herceptin has been approved for use in breast cancer. Other agents, such as SU101 and CGP 57418B, are well into phase I-III trials. Newer, more selective tyrosine kinase inhibitors are being evaluated for future use in the treatment of hematologic and solid tumors as well as a wide range of inflammatory or autoimmune diseases.