James Blake

Inhibition of Growth Factor Signaling by Small-Molecule Inhibitors of ErbB, Raf,and MEK

Approval of Gleevec and its demonstrated therapeutic value marked the full recognition of kinase inhibitorsas a relevant means of cancer treatment. A significant number of kinase inhibitors have recentlyentered clinical practice for the treatment of a variety of cancers and many others are in advancedstages of clinical research. Among these are several promising agents that act in the pathway that initiateswith the growth factor receptors EGFR/ErbB2 and signals through Raf and MEK to the MAP kinase ERK. Thischapter focuses on the biological rationale, enzymatic and pharmacological properties, and clinical statusof several inhibitors of EGFR/ErbB2, Raf, and MEK1/2. Coverage is given of those compounds that have gainedapproval or are being evaluated in human clinical trials.