Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan 48109-5934, USA.
J Surg Oncol. 2011 Dec;104(8):901-6. doi: 10.1002/jso.21872.
Progression on first-line therapy with imatinib in gastrointestinal stromal tumors (GIST) is caused by either initial resistance or more often a secondary mutation in tyrosine kinases KIT or PDGFR. Therapies in development for imatinib-resistant GIST include agents that target KIT/PDGFR with greater potency or possess broader kinase inhibition profiles including VEGFR. To circumvent secondary mutations in KIT/PDGFR, inhibition of the downstream signaling in PI3K/Akt/mTOR pathway and enhanced degradation of KIT/PDGFR are also under investigation.
胃肠道间质肿瘤（GIST）一线治疗中伊马替尼的进展是由于初始耐药或更常见的酪氨酸激酶 KIT 或 PDGFR 中的继发突变引起的。针对伊马替尼耐药 GIST 的开发中的治疗方法包括具有更高效力或具有更广泛的激酶抑制谱（包括 VEGFR）的靶向 KIT/PDGFR 的药物。为了避免 KIT/PDGFR 的继发突变，还在研究 PI3K/Akt/mTOR 通路的下游信号抑制和增强 KIT/PDGFR 的降解。
