Sarcoma Unit, Royal Marsden Hospital, United Kingdom ; Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
Onco Targets Ther. 2013 Jul 30;6:1011-23. doi: 10.2147/OTT.S31260. Print 2013.
Gastrointestinal stromal tumors (GISTs) are the most common sarcoma of the gastrointestinal tract, with transformation typically driven by activating mutations of c-KIT and less commonly platelet-derived growth factor receptor alpha (PDGFRA). Successful targeting of c-KIT and PDGFRA with imatinib, a tyrosine kinase inhibitor (TKI), has had a major impact in advanced GIST and as an adjuvant and neoadjuvant treatment. If treatment with imatinib fails, further lines of TKI therapy have a role, but disease response is usually only measured in months, so strategies to maximize the benefit from imatinib are paramount. Here, we provide an overview of the structure and signaling of c-KIT coupled with a review of the clinical trials of imatinib in GIST. In doing so, we make recommendations about the duration of imatinib therapy and suggest how best to utilize imatinib in order to improve patient outcomes in the future.
胃肠道间质瘤（GISTs）是胃肠道最常见的肉瘤，其转化通常由 c-KIT 的激活突变驱动，较少见的由血小板衍生生长因子受体α（PDGFRA）驱动。伊马替尼是一种酪氨酸激酶抑制剂（TKI），成功地靶向 c-KIT 和 PDGFRA，对晚期 GIST 以及辅助和新辅助治疗产生了重大影响。如果伊马替尼治疗失败，进一步的 TKI 治疗方案仍有作用，但疾病反应通常只能持续数月，因此最大限度地从伊马替尼中获益的策略至关重要。在这里，我们概述了 c-KIT 的结构和信号传导，并回顾了伊马替尼在 GIST 中的临床试验。通过这样做，我们就伊马替尼治疗的持续时间提出了建议，并就如何最好地利用伊马替尼以改善未来患者的预后提出了建议。
