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.
Chen
Lei L
LL
Department of Sarcoma, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. llchen@mdanderson.org
Sabripour
Mahyar
M
Andtbacka
Robert H I
RH
Patel
Shreyaskumar R
SR
Feig
Barry W
BW
Macapinlac
Homer A
HA
Choi
Haesun
H
Wu
Elsie F
EF
Frazier
Marsha L
ML
Benjamin
Robert S
RS
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D046152:Gastrointestinal Stromal Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D020125:Mutation, Missense; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*; D011859:Radiography
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit