在21世纪初之前，由于缺乏有效的治疗方法，晚期胃肠间质瘤（GIST）患者的预后非常差。2000年代初期酪氨酸激酶抑制剂的发展显著改善了GIST患者的总体生存率。酪氨酸激酶抑制剂治疗GIST的第一次临床试验中，依马替尼获得了极大的成功，因此被批准作为晚期GIST的一线治疗；这项研究开放给所有人参加，并不限于任何GIST亚型。导致获得晚期GIST二线、三线和四线治疗批准的试验也开放给所有晚期/转移的GIST患者。只有在后来的回顾性分析中，我们才意识到分子亚型在这些研究中所起的作用。在这篇综述中，我们讨论了导致美国食品和药物管理局批准依马替尼（一线）、舒尼替尼（二线）、雷格拉非尼（三线）和雷普替尼（四线）用于治疗晚期KIT突变GIST的研究。此外，我们还回顾了关于GIST分子亚型的信息如何被用于加速其他针对非KIT突变GIST的靶向治疗药物的批准，导致批准了5种针对特定GIST分子亚型治疗的附加药物。我们还讨论了分子亚型的理解将如何在治疗晚期GIST的下一代治疗方法中发挥作用。 © 2023。这是美国政府的工作，不受版权保护;外国版权保护可能适用。

Prior to the early 2000s, patients with advanced gastrointestinal stromal tumors (GIST) had very poor prognoses owing to a lack of effective therapies. The development of tyrosine kinase inhibitors at the turn of the century significantly improved the overall survival for patients with GIST. The resounding success of imatinib in the first clinical trial of a tyrosine kinase inhibitor to treat GIST led to its approval for first-line therapy for advanced GIST; this study was open to all comers and not restricted to any GIST subtype(s). The trials that led to the approvals of second-, third-, and fourth-line therapy for advanced GIST were also open to all patients with advanced/metastatic GIST. Only in retrospect do we realize the role that the molecular subtypes played in the results observed in these studies. In this review, we discuss the studies that led to the US Food and Drug Administration approval of imatinib (first line), sunitinib (second line), regorafenib (third line), and ripretinib (fourth line) for advanced KIT-mutant GIST. In addition, we review how information about GIST molecular subtypes has been used to accelerate the approval of other targeted therapies for non-KIT mutant GIST, leading to the approval of five additional drugs indicated for the treatment of specific GIST molecular subtypes. We also discuss how our understanding of the molecular subtypes will play a role in the next generation of therapeutic approaches for treating advanced GIST.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.