STI571 (Gleevec) as a paradigm for cancer therapy.
STI571 (Gleevec, imatinib mesylate) exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of a specific cancer. This article reviews the identification of Bcr-Abl as a therapeutic target in chronic myelogenous leukemia and the steps in the development of an agent to inactivate this abnormality. Issues related to clinical trials of molecularly targeted agents are discussed, including dose and patient selection and possible mechanisms of resistance to STI571. Finally, the potential use of STI571 with different tumors and the translation of this paradigm to other malignancies are explored.
Druker
Brian J
BJ
Leukemia Center, Oregon Health & Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA. drukerb@ohsu.edu
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016044:Fusion Proteins, bcr-abl / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl