Targeting oncogene dependence and resistance.
Our expanding experience with imatinib mesylate provides instructive lessons on the power and pitfalls of targeted therapy. The often impressive initial clinical responses seen with imatinib in a variety of malignancies inevitably give way to the emergence of resistant disease. Recent findings reveal several mechanisms of resistance and suggest ways to overcome them.
Hingorani
Sunil R
SR
Abramson Family Cancer Research Institute, Abramson Cancer Center of the University of Pennsylvania School of Medicine, Department of Medicine, Philadelphia 19104, USA. srhingo@mail.med.upenn.edu
Tuveson
David A
DA
D000483:Alleles; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009857:Oncogenes / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl