TY - JOUR
T1 - Targeted therapy in chronic myeloid leukemia
AU - Jabbour, Elias
AU - Cortes, Jorge E.
AU - Ghanem, Hady
AU - O'Brien, Susan
AU - Kantarjian, Hagop M.
N1 - Funding Information:
Hagop M Kantarjian has received research grants from Novartis Oncology and Bristol-Myers Squibb; Jorge E Cortes has received research grants from Novartis Oncology, Bristol-Myers Squibb and Wyeth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Chronic myeloid leukemia
KW - Dasatinib
KW - Imatinib
KW - Nitotinib
UR - http://www.scopus.com/inward/record.url?scp=38349016567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38349016567&partnerID=8YFLogxK
U2 - 10.1586/14737140.8.1.99
DO - 10.1586/14737140.8.1.99
M3 - Review article
C2 - 18095887
AN - SCOPUS:38349016567
SN - 1473-7140
VL - 8
SP - 99
EP - 110
JO - Expert Review of Anticancer Therapy
JF - Expert Review of Anticancer Therapy
IS - 1
ER -