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Choosing the Best Second-Line Tyrosine Kinase Inhibitor in Imatinib- Resistant Chronic Myeloid Leukemia Patients Harboring Bcr-Abl Kinase Domain Mutations: How Reliable Is the IC50?
- Source :
- Oncologist; Jun2011, Vol. 16 Issue 6, p868-876, 9p, 1 Chart
- Publication Year :
- 2011
-
Abstract
- Development of drug resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients is often accompanied by selection of point mutations in the kinase domain (KD) of the Bcr-Abl oncoprotein, where imatinib binds. Several second-generation tyrosine kinase inhibitors (TKIs) have been designed rationally so as to enhance potency and retain the ability to bind mutated forms of Bcr-Abl. Since the preclinical phase of their development, most of these inhibitors have been tested in in vitro studies to assess their half maximal inhibitory concentration (IC<subscript>50</subscript>) for unmutated and mutated Bcr-Abl--that is, the drug concentration required to inhibit the cell proliferation or the phosphorylation processes driven by either the unmutated or the mutated forms of the kinase. A number of such studies have been published, and now that two inhibitors--dasatinib and nilotinib--are available for the treatment of imatinib-resistant cases, it is tempting for clinicians to reason on the IC<subscript>50</subscript> values to guess, case by case, which one will work best in patients harboring specific Bcr-Abl KD mutations. Here, we discuss the pros and cons of using this approach in TKI selection. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10837159
- Volume :
- 16
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Oncologist
- Publication Type :
- Academic Journal
- Accession number :
- 62543107
- Full Text :
- https://doi.org/10.1634/theoncologist.2010-0388