The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor.
The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor.
复制标题
DOI：
10.1200/edbk_351231
复制
发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
胃肠道间质瘤（GIST）是最常见的间叶来源的恶性肿瘤，是合理开发分子靶向药物的一个引人注目的临床和生物学模型。这是因为大多数GIST由KIT或PDGFRA受体酪氨酸激酶的功能获得性突变驱动。特定的GIST突变限定了明确的分子亚组，这些亚组必须在诊断检查期间确定，以指导临床管理，包括治疗决策。手术是局部疾病的基础治疗，在转移性疾病中也具有临床意义。靶向药物和外科手术的正确组合和顺序可改善GIST患者的结局，应在多学科专家团队中单独讨论。目前批准的所有治疗GIST的药物均基于口服酪氨酸激酶抑制剂，靶向KIT和PDGFRA致癌激活。虽然一线伊马替尼实现了显着的长期疾病控制，后续治疗线的好处是更温和的。新的治疗策略集中于克服KIT或PDGFRA继发突变的异质性，并提供对特定挑战性突变的更有效抑制。本文综述了目前对GIST的认识和治疗，重点介绍了最新进展。
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.