Imatinib resistance in gastrointestinal stromal tumors.
Conventional chemotherapeutic drugs are ineffective in treatment of gastrointestinal stromal tumors (GISTs). Imatinib (STI571, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs. Unfortunately, imatinib resistance has emerged. The reported mechanism of imatinib resistance in GISTs involves missense mutation in the kinase domain of KIT, including Thr670Ile, Tyr823Asp, and Val654Ala. The established mechanisms and potential mechanisms of imatinib resistance in GISTs, the imaging studies indicative of early development of imatinib resistance, and the management of imatinib-resistant GISTs are discussed.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T2 T3 T4 T5 T6 T7 T8 T9
CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-N CHEMICAL GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
Imatinib KIT ABL BCR ABL PDGFRA PDGFRB, kinase domain KIT, Thr670Ile Imatinib Tyr823Asp Val654Ala STI571 Gleevec Glivec imatinib imatinib imatinib imatinib imatinib