Signal transduction therapy in haematological malignancies: identification and targeting of tyrosine kinases.
Tyrosine kinases play key roles in cell proliferation, survival and differentiation. Their aberrant activation, caused either by the formation of fusion genes by chromosome translocation or by intragenic changes, such as point mutations or internal duplications, is of major importance in the development of many haematological malignancies. An understanding of the mechanisms by which BCR-ABL contributes to the pathogenesis of chronic myeloid leukaemia led to the development of imatinib, the first of several tyrosine kinase inhibitors to enter clinical trials. Although the development of resistance has been problematic, particularly in aggressive disease, the development of novel inhibitors and combination with other forms of therapy shows promise.
Chase
Andrew
A
Wessex Regional Genetics Laboratory, Salisbury and Human Genetics Division, University of Southampton, Salisbury District Hospital, Salisbury SP2 8BJ, U.K.
Cross
Nicholas C P
NC
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases