TY - JOUR
T1 - Imatinib as a paradigm of targeted therapies
AU - Druker, Brian J.
PY - 2004
Y1 - 2004
N2 - Imatinib (Gleevec) exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of a specific cancer. This article reviews the identification of the BCR-ABL tyrosine kinase as a therapeutic target in chronic myeloid leukemia and the steps in the development of an agent to specifically inactivate this abnormality. The clinical trials results are reviewed along with a description of resistance mechanisms. As imatinib also inhibits the tyrosine kinase activity of KIT and the platelet-derived growth factor receptors, the extension of imatinib to malignancies driven by these kinases will be described. Issues related to clinical trials of molecularly targeted agents are discussed, including patient and dose selection. Last, the translation of this paradigm to other malignancies is explored.
AB - Imatinib (Gleevec) exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of a specific cancer. This article reviews the identification of the BCR-ABL tyrosine kinase as a therapeutic target in chronic myeloid leukemia and the steps in the development of an agent to specifically inactivate this abnormality. The clinical trials results are reviewed along with a description of resistance mechanisms. As imatinib also inhibits the tyrosine kinase activity of KIT and the platelet-derived growth factor receptors, the extension of imatinib to malignancies driven by these kinases will be described. Issues related to clinical trials of molecularly targeted agents are discussed, including patient and dose selection. Last, the translation of this paradigm to other malignancies is explored.
UR - http://www.scopus.com/inward/record.url?scp=4344623889&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4344623889&partnerID=8YFLogxK
U2 - 10.1016/S0065-230X(04)91001-9
DO - 10.1016/S0065-230X(04)91001-9
M3 - Article
C2 - 15327887
AN - SCOPUS:4344623889
SN - 0065-230X
VL - 91
SP - 1
EP - 30
JO - Advances in cancer research
JF - Advances in cancer research
ER -