Gleevec and the New Generation of Molecular-Targeting Therapy

Gleevec and the New Generation of Molecular-Targeting Therapy

Miniaci Performing Arts Center

The purpose of this literature research project is to investigate the therapeutic roles of Gleevec applied to the treatment of various cancers as a tyrosine-kinase inhibitor. In the 1970s it was shown that Chronic Myeloid Leukemia (CML), a blood cancer, was the byproduct of translocation of the chromosome 9 q-arm (abl gene) with the chromosome 22 q-arm (bcr gene). The new gene that formed, brc-abl, was referred to as the Philadelphia gene (Ph). The abnormal protein that forms from Ph gene, BCR-ABL, is what causes CML. BRC-ABL was shown to be a tyrosine kinase. With this knowledge, much research was done to discover a way to interrupt and/or stop the activities of BCR- ABL. The new drug that came out of this research was STI-571, also referred to as imatinib mesylate and more popularly as Gleevec. Gleevec has an amazing ability to stop BCR-ABL activities, by binding to its inactive form as a competitive inhibitor, with little to no side affects while causing an increase in hematological responses. It was soon discovered that Gleevec inhibition abilities affected other tyrosine kinases such as PDGF, c-kit, and β-catenin. New studies are being done to discover if Gleevec can be used as frontline therapy for other cancers such as osteosarcoma, lung, and colon on its own or in combination with other drugs. Research is also being done to strengthen Gleevec’s inhibition abilities and discover new drugs that can stop cancer mutations for which Gleevec has previously had little or no effect.