胃肠间质瘤诊治的成功对其他消化道肿瘤的启示

The enlightenment of success in diagnosis and treatment of gastrointestinal stromal tumor to other digestive malignant tumors

胃肠间质瘤(gastrointestinal stromal tumor,GIST)作为最早开始接受小分子酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗的实体瘤,在精准治疗实施过程中获得了很大的成功,是实体瘤精准治疗的典范,其成功经验对其他实体瘤的诊疗具有非常重要的启示。首先,利用特异性的驱动基因突变将GIST成功从其他软组织肉瘤中区分开来,开启了利用分子特征将实体瘤进行亚组划分的时代;其次,c-kit基因功能性突变的发现与其特异性抑制剂的研发提示靶向治疗最重要的核心在于特异性驱动基因的寻找与确认;伊马替尼是首个批准辅助治疗实体瘤的TKI,停药后复发提示TKI辅助治疗到底是可以根治实体瘤还是仅仅推迟了肿瘤复发这一问题暂时还没有答案;TKI耐药后新的突变基因的出现为探索TKI耐药原因提供了新的机制;而新的实体瘤疗效评价方法——Choi标准被广泛认可,揭示了传统的RECIST标准并不适合靶向药物的疗效评估。这些新的问题与现象对其他消化道肿瘤的诊治具有重要的借鉴意义。

As the model of solid tumor receiving tyrosine kinase inhibitor （TKI） therapy, gastrointestinal stromal tumor （GIST） succeeded in precision treatment. The success of GIST will be significant to other solid tumors. Firstly, identifying oncogenic driver gene seperated GIST from other sarcoma diseases. It startecl the era of subgrouping solid tumor for treatment based on molecular features. Secondly, the founding of c-kit mutation and development of imatinib indicated the most important thing of targeted therapy is to search and confirm specific driver mutation. Imatinib is the first targeted agent to be used in adjuvant therapy. The phenomenon of tumor recurrence after imatinib withdrawal demonstrated that it is still questionable whether TKI adjuvant therapy can cure tumor or just delay the time of recurrence. Meanwhile, the genetic secondary mutation after tumor progression revealed the new mechanism of TKI resistance. A new standard of efficacy assessment named Choi criterion was accepted wildly and showed the traditional RECIST criterion was not applicable for the efficacy evaluation of targeted agency. These new questions and phenomenon are very important to diagnoses and treatment of other digestive malignant tumors.