Targeted therapy in chronic myeloid leukemia.
Chronic myeloid leukemia (CML) is characterized by the formation of the Philadelphia chromosome and oncogenic signaling by the resulting Bcr-Abl fusion protein. Understanding the molecular basis of CML has led to the development of highly effective targeted therapies that block Bcr-Abl tyrosine kinase activity. Imatinib, the current first-line therapy for CML, induces durable treatment responses in most patients. However, patients may develop imatinib resistance, which is often due to BCR-ABL mutations. With the availability of second generation tyrosine kinase inhibitors, an effective therapeutic option other than stem cell transplantation is available following imatinib failure. Randomized trial data suggest that dasatinib treatment is superior to imatinib dose escalation in patients with imatinib resistance. Nilotinib, a recently approved analogue of imatinib, has also demonstrated encouraging treatment responses in patients with imatinib-resistant CML. Other agents (including bosutinib and INNO-406) are in clinical development. With the potential availability of multiple treatment options for patients with CML, it may be possible to tailor treatment according to individual patient or disease characteristics, for example, BCR-ABL mutations. Future CML treatment may involve combination strategies. Overall, targeted agents have significantly improved the prognosis of patients diagnosed with CML.
Jabbour
Elias
E
The University of Texas MD Anderson Cancer Center, Department of Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030, USA. ejabbour@mdanderson.org
Cortes
Jorge E
JE
Ghanem
Hady
H
O'Brien
Susan
S
Kantarjian
Hagop M
HM
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics / Q000628:therapy*
D000970:Antineoplastic Agents