The New Wonder Drug of Cancer Therapy

Tyrosine kinase activation has long been known to be an important mechanism under-lying tumor development, proliferation and local spread.1 Inhibitors of these kinases have, therefore, been attractive targets of anti-cancer therapies.2 The toxicity of non-selective tyrosine kinase inhibitors, however, has severely limited their use for clinical applications, leading to the search for “designer ” inhibitors that selectively block specific groups of tyrosine kinases. By being more selective, these agents retain their anti-cancer activities while having a lower incidence of side effects. Perhaps the most promising agent that has emerged thus far has been STI-571 (a.k.a., Imatinib Mesylate, Gleevec©), while other tyrosine kinase inhibitors are at different stages of clinical trials.3 STI-571 is a low-molecular weight compound that binds to the phosphorylation pocket of specific tyrosine kinases. Initially designed to inhibit the oncogene c-Abl, STI-571 was also found to selectively inhibit cKit as well as PDGFrα and PDGFrβ. Its first clinical application was in the treatment of chronic myelogenous leukemia (CML), where the translocation giving rise to the Philadelphia Chromosome results in a Bcr-Abl fusion protei