Current and emerging treatment options in chronic myeloid leukemia.
Treatments for chronic myeloid leukemia (CML) represent a success story in molecular medicine. The development of imatinib, a tyrosine kinase inhibitor (TKI) targeted against the causative Bcr-Abl oncoprotein in CML, has resulted in hematologic and cytogenetic remissions in all phases of CML. A significant proportion of patients are resistant to imatinib or develop resistance during treatment. This is often a result of mutated forms of the Bcr-Abl oncoprotein to which imatinib is unable to bind. Several strategies have been developed to overcome the problem of imatinib resistance, including high-dose imatinib, novel targeted agents, and combination treatments. Novel agents include dasatinib, a potent TKI that inhibits several critical oncogenic proteins and which has recently been approved for patients with CML who are resistant or intolerant to imatinib; and nilotinib, a potent selective Bcr-Abl kinase inhibitor currently in clinical development. Other agents in development include SKI-606 and INNO-406. Stem cell transplantation remains a useful option, although it is not generally used as first-line treatment. Overall, there are an increasing number of treatment options available for patients with CML.
Jabbour
Elias
E
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cortes
Jorge E
JE
Giles
Francis J
FJ
O'Brien
Susan
S
Kantarjian
Hagop M
HM
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate