Is there a cloud in the silver lining for imatinib?
Imatinib mesylate (Gleevec) or Glivec), a small molecule tyrosine kinase inhibitor for the treatment of chronic myeloid leukaemia, has been said to herald the dawn of a new era of rationally designed, molecularly targeted oncotherapy. Lurking on the same new horizon, however, is the age-old spectre of drug resistance. This review sets the intoxicating clinical perspective against the more sobering laboratory evidence of such divergent mechanisms of imatinib resistance as gene amplification and stem cell quiescence. Polychemotherapy has already been considered to combat resistance, but a more innovative, as yet unformulated, approach may be advocated.
Paterson
S C
SC
Department of Bioscience, Royal College, University of Strathclyde, Glasgow, UK.
Smith
K D
KD
Holyoake
T L
TL
Jørgensen
H G
HG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016044:Fusion Proteins, bcr-abl; D005784:Gene Amplification; D019450:Genes, MDR; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects; D009961:Orosomucoid / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D009961:Orosomucoid; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D000255:Adenosine Triphosphate; D016044:Fusion Proteins, bcr-abl