Towards a pharmacologically guided individualization of imatinib and sunitnib therapy

Abstract

The approval of imatinib mesylate (Gleeve) in 2001 has added a new class of drugs to the systemic treatment of cancer: that of the tyrosine kinase inhibitors (TKIs). Imatinib inhibits autophosphorylation of specific proteins involved in oncogenesis such as the BCR-ABL fusion protein (expressed in Philadelphia chromosome positive chronic myeloid leukemia), c-KIT (expressed in gastrointestinal stromal tumors; GIST) and the plateletderived growth factor receptor (PDGFR; i.e. expressed in GIST and several sarcomas). After a decade of therapeutic use, imatinib has proven to be a highly effective targeted agent with a median overall survival in advanced GIST patients close to 5 years