Translation of the Philadelphia chromosome into therapy for CML.
Throughout its history, chronic myeloid leukemia (CML) has set precedents for cancer research and therapy. These range from the identification of the first specific chromosomal abnormality associated with cancer to the development of imatinib as a specific, targeted therapy for the disease. The successful development of imatinib as a therapeutic agent for CML can be attributed directly to decades of scientific discoveries. These discoveries determined that the BCR-ABL tyrosine kinase is the critical pathogenetic event in CML and an ideal target for therapy. This was confirmed in clinical trials of imatinib, with imatinib significantly improving the long-term survival of patients with CML. Continuing in this tradition of scientific discoveries leading to improved therapies, the understanding of resistance to imatinib has rapidly led to strategies to circumvent resistance. Continued studies of hematologic malignancies will allow this paradigm of targeting molecular pathogenetic events to be applied to many additional hematologic cancers.
Druker
Brian J
BJ
Howard Hughes Medical Institute, Oregon Health & Science University Cancer Institute, Portland, USA. drukerb@ohsu.edu
D001549:Benzamides; D035843:Biomedical Research / Q000266:history; D016503:Drug Delivery Systems / Q000266:history / Q000379:methods; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000266:history; D010677:Philadelphia Chromosome / Q000187:drug effects; D010879:Piperazines / Q000266:history / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000266:history / Q000494:pharmacology
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases