title: It's about time: lessons for solid tumors from chronic myelogenous leukemia therapy.
abstract: The use of imatinib in chronic myelogenous leukemia (CML) transformed the disease, rapidly changing the median survival from 4 years to at least 20 years. In this review, we outline the causes of this revolution, including the identification of a critical driving molecular aberration, BCR-ABL, and the development of a potent and specific inhibitor, imatinib. Equally important was the timing of the targeted therapy, specifically its administration to patients with newly diagnosed disease. In solid tumors, targeted therapies are often both developed and used in metastatic malignancies after conventional approaches have failed. We postulate that this strategy is similar to using imatinib in blast-crisis CML, in which response rates are less than 15%, all patients relapse, and median survival remains only about 1 year. We hypothesize that the imatinib-led revolution in CML, including the critically important factor of timing, may be applicable to other cancers as well. Therefore, it will be important to use promising targeted therapies in the earliest phases of biomarker-defined solid tumors, before metastatic progression, to determine if outcomes can be significantly improved and, thus, establish if the success of imatinib in CML is an anomaly or a paradigm.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston TX 77030, USA. jwestin@mdanderson.org
authors.forename: Jason R
authors.initials: JR
authors.lastname: Westin
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate