Takahashi Shunji
Dept. of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research.
Gan To Kagaku Ryoho. 2017 Jun;44(6):457-462.
Soft tissue sarcoma(STS)is one of the rare and intractable cancers, and most types of STS are not sensitive to chemotherapy. Development of specific molecular target therapy for each type of STS is necessary. There are specific chromosome translocations in 20-30% of STS, but their products are mostly transcriptional factors, and target therapy for those factors are difficult to develop. Trabectedin is an alkylating agent and is also inhibit function of transcriptional factors, and shows efficacy for translocation-related sarcoma(TRS)such as myxoid liposarcoma. As molecular target therapies for gene mutations, success in molecular target therapy for c-kit and PDGFR mutation in GIST was followed by efficacy for rare sarcomas such as IMT or DFSP, but there are few developments in other sarcomas. STSs are frequently associated with angiogenesis and angiogenesis inhibitors such as pazopanib show some efficacy. Then immune checkpoint inhibitors also have been developed.
软组织肉瘤(STS)是一种罕见且难治的癌症,大多数类型的STS对化疗不敏感。针对每种类型的STS开发特异性分子靶向治疗是必要的。20%-30%的STS存在特异性染色体易位,但其产物大多为转录因子,针对这些因子的靶向治疗难以开发。曲贝替定是一种烷化剂,也能抑制转录因子的功能,对黏液样脂肪肉瘤等易位相关肉瘤(TRS)显示出疗效。作为针对基因突变的分子靶向治疗,胃肠道间质瘤(GIST)中c-kit和血小板衍生生长因子受体(PDGFR)突变的分子靶向治疗取得成功后,炎性肌纤维母细胞瘤(IMT)或隆突性皮肤纤维肉瘤(DFSP)等罕见肉瘤也显示出疗效,但其他肉瘤的相关进展较少。STS常与血管生成相关,帕唑帕尼等血管生成抑制剂显示出一定疗效。随后免疫检查点抑制剂也得到了开发。