文章：

未分化多形性肉瘤的遗传异质性：靶向治疗是否存在潜力？

Genetic Heterogeneity of Undifferentiated Pleomorphic Sarcoma: Is There Potential for Targeted Therapy?

原文发布日期：10 November 2025

DOI: 10.3390/cancers17223613

类型: Article

开放获取: 是

英文摘要：

Undifferentiated pleomorphic sarcoma (UPS) is the most morphologically and genetically heterogeneous form of soft tissue sarcoma. UPS tumors can exhibit a wide range of genetic abnormalities, including activating and inactivating mutations, gene amplifications, chromosomal translocations, and copy number variations. Owing to this extensive genetic heterogeneity, no UPS-specific therapeutic targets have yet been validated, complicating diagnosis, prognosis, and the selection of targeted treatment strategies. Currently, immune checkpoint inhibitors (targeting PD-1, PD-L1, and CTLA-4) are the only validated targeted therapy for UPS, reflecting the frequent mutational events that activate immune response pathways. Because molecular genetic profiling alone provides limited prognostic value for chemoresistance in UPS, the development of experimental ex vivo and in vitro testing approaches may help to identify and exclude potentially ineffective targeted therapies.

摘要翻译： 

未分化多形性肉瘤是软组织肉瘤中形态学和遗传学异质性最高的亚型。该肿瘤可呈现广泛的遗传学异常，包括激活性和失活性突变、基因扩增、染色体易位以及拷贝数变异。由于这种广泛的遗传异质性，目前尚未验证出未分化多形性肉瘤的特异性治疗靶点，这使其诊断、预后评估及靶向治疗策略的选择变得复杂。目前，免疫检查点抑制剂（靶向PD-1、PD-L1和CTLA-4）是唯一经过验证的未分化多形性肉瘤靶向疗法，这反映了该肿瘤中频繁激活免疫应答通路的突变事件。鉴于单纯分子遗传学分析对未分化多形性肉瘤化疗耐药性的预后价值有限，开发实验性离体和体外检测方法可能有助于识别并排除潜在无效的靶向治疗方案。

原文链接：

Genetic Heterogeneity of Undifferentiated Pleomorphic Sarcoma: Is There Potential for Targeted Therapy?