First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece.
Oncology Unit, 2nd Department of Medicine, Medical School, Hippocratio General Hospital of Athens, National and Kapodistrian University of Athens, V. Sofias 114, 11527 Athens, Greece.
Cells. 2023 Nov 15;12(22):2632. doi: 10.3390/cells12222632.
Genomic profiling has improved our understanding of the pathogenesis of different cancers and led to the development of several targeted therapies, especially in epithelial tumors. In this review, we focus on the clinical utility of next-generation sequencing (NGS) to inform therapeutics in soft tissue sarcoma (STS). The role of NGS is still controversial in patients with sarcoma, given the low mutational burden and the lack of recurrent targetable alterations in most of the sarcoma histotypes. The clinical impact of genomic profiling in STS has not been investigated prospectively. A limited number of retrospective, mainly single-institution, studies have addressed this issue using various NGS technologies and platforms and a variety of criteria to define a genomic alteration as actionable. Despite the detailed reports on the different gene mutations, fusions, or amplifications that were detected, data on the use and efficacy of targeted treatment are very scarce at present. With the exception of gastrointestinal stromal tumors (GISTs), these targeted therapies are administered either through off-label prescription of an approved drug or enrollment in a matched clinical trial. Based mainly on anecdotal reports, the outcome of targeted therapies in the different STS histotypes is discussed. Prospective studies are warranted to assess whether genomic profiling improves the management of STS patients.
基因组分析提高了我们对不同癌症发病机制的认识，并促成了几种靶向治疗方法的发展，特别是在上皮肿瘤中。在这篇综述中，我们重点关注下一代测序（NGS）在软组织肉瘤（STS）治疗中的临床应用。鉴于大多数肉瘤组织类型的突变负担较低且缺乏可重复的靶向改变，NGS 在肉瘤患者中的作用仍存在争议。基因组分析在 STS 中的临床影响尚未进行前瞻性研究。少数回顾性的、主要是单机构的研究使用各种 NGS 技术和平台，并采用各种标准来定义可操作的基因组改变，解决了这个问题。尽管详细报告了检测到的不同基因突变、融合或扩增，但目前关于靶向治疗的使用和疗效的数据非常有限。除了胃肠道间质瘤（GIST）外，这些靶向治疗要么通过批准药物的标签外处方，要么通过参加匹配的临床试验来进行。主要根据传闻报告，讨论了不同 STS 组织类型中靶向治疗的结果。需要进行前瞻性研究来评估基因组分析是否能改善 STS 患者的治疗效果。
