Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Department of Surgery, University of Pennsylvania, Philadelphia, PA.
Am Soc Clin Oncol Educ Book. 2022 Apr;42:1-15. doi: 10.1200/EDBK_351231.
Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin and a compelling clinical and biologic model for the rational development of molecularly targeted agents. This is because the majority of GISTs are driven by gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinases. Specific GIST mutations circumscribe well-defined molecular subgroups that must be determined during the diagnostic work-up to guide clinical management, including therapeutic decisions. Surgery is the cornerstone treatment in localized disease and can also be clinically relevant in the metastatic setting. The correct combination and sequence of targeted agents and surgical procedures improves outcomes for patients with GIST and should be discussed individually within multidisciplinary expert teams. All currently approved agents for the treatment of GIST are based on orally available tyrosine kinase inhibitors targeting KIT and PDGFRA oncogenic activation. Although first-line imatinib achieves remarkable prolonged disease control, the benefit of subsequent lines of treatment is more modest. Novel therapeutic strategies focus on overcoming the heterogeneity of KIT or PDGFRA secondary mutations and providing more potent inhibition of specific challenging mutations. This article reviews the current understanding and treatment of GIST, with an emphasis on recent advances.
胃肠道间质瘤（GIST）是最常见的源自间叶组织的恶性肿瘤，也是合理开发针对分子靶点药物的极具说服力的临床和生物学模型。这是因为大多数 GIST 是由 KIT 或 PDGFRA 受体酪氨酸激酶的功能获得性突变驱动的。特定的 GIST 突变划定了明确的分子亚组，在诊断工作中必须确定这些亚组，以指导临床管理，包括治疗决策。手术是局限性疾病的基石治疗方法，在转移性疾病中也具有临床相关性。正确组合和顺序使用靶向药物和手术程序可改善 GIST 患者的预后，并且应在多学科专家团队中进行个体化讨论。目前所有批准用于治疗 GIST 的药物均基于针对 KIT 和 PDGFRA 致癌激活的口服可用酪氨酸激酶抑制剂。虽然一线伊马替尼可显著延长疾病控制时间，但后续治疗线的获益更为有限。新的治疗策略侧重于克服 KIT 或 PDGFRA 继发突变的异质性，并提供针对特定挑战性突变的更有效的抑制。本文综述了 GIST 的当前认识和治疗方法，重点介绍了最新进展。
