itor Drug Resistance in Chronic Myelogenous Leukemia

ownload pite the initial effectiveness of oncogene-directed cancer therapeutics, acquired drug resistance rethe ultimate “Achilles' heel” for long-term durable remission in cancer patients. Acquisition of drug nce is not more evident elsewhere than in the use of tyrosine kinase inhibitors, imatinib and da, for patients with chronic myelogenous leukemia. Hence, even though imatinib initially produces ion in the chronic phase, ultimately these therapeutics fail via the emergence of drug resistance, in chronic myelogenous leukemia could inevitably progress to a terminal blast phase culminating in utcome. Technically, it is challenging to predict the onset of drug resistance in a small number of ene-transformed cells, making the decision of when and how to employ second-generation tyrosine inhibitors, or employ novel compounds that would be of benefit in treating drug-resistant Bcr-Abl ts mainly retrospective. Here, we characterize a rapid and sensitive real-time fluorescent resonance transfer–based assay that is able to detect the in vivo activity of Bcr-Abl and its inhibition by small ule compounds. Due to its real-time and in vivo nature, such an approach has the potential to monmolec itor a drug-resistant phenotype, as well as to identify pharmaceutical agents that inhibit drug-resistant Bcr-Abl oncoproteins in vivo. Mol Cancer Ther; 9(11); OF1–9. ©2010 AACR.