Refining targeted therapies in chronic myeloid leukemia: development and application of nilotinib, a step beyond imatinib
Massimo Breccia, Giuliana Alimena
Department of Cellular Biotechnology and Hematology, “Sapienza” University of Rome, Italy
Abstract: The BCR-ABL kinase inhibitor imatinib mesylate is currently the standard therapy for patients with chronic myeloid leukemia (CML). Despite the remarkable results achieved with imatinib for the treatment of CML, the emergence of resistance to this drug has become a significant problem. Mutations within the ABL kinase domain have been identified as the main mechanism of resistance to imatinib. Other mechanisms include genomic amplification of BCR-ABL and modulation of drug efflux or influx transporters. Several strategies have been developed to overcome the problem of imatinib resistance, including dose escalation of imatinib, combination treatments, or novel targeted agents. Nilotinib is a tyrosine kinase inhibitor 30-fold more potent than imatinib, active against a wide range of mutant clones, except T315I. Phase I–II trials of nilotinib showed high activity in imatinib-resistant CML and Ph+ acute lymphoblastic leukemia. We here review the development of nilotinib and the activity of this agent in CML patients and in other forms of sensitive neoplasms.
Keywords: myeloid leukemia, nilotinib, imatinib, neoplasms
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF]