Background/Objectives: Soft tissue sarcomas (STSs) are rare tumors arising from mesenchymal tissues, comprising over 100 distinct histological subtypes with varying biological behaviors, metastatic patterns, and treatment responses Despite advances in multimodal therapy, the overall survival of patients with metastatic STS is poor, mainly due to the weak response to conventional chemotherapy based on doxorubicin and ifosfamide.Methods: This review examines the evolution from traditional one-size-fits-all treatments to personalized medicine strategies, primarily focusing on assays based on patient-derived tumor samples, and it highlights their emerging role in guiding personalized treatment decisions and improving clinical outcomes in STS. These approaches, also known as functional precision oncology, are a step closer to the clinical situation as compared to other personalized therapies that rely on the identification of targetable genomic alterations using high-throughput technologies such as whole-genome sequencing, which have thus far failed to show convincing responses in STS treatment.Results: The main functional precision oncology platforms tested in patients with STS are in vitro cell viability tests, organoid cultures, and patient-derived xenografts. Each has advantages and limitations. In this context, in vitro drug sensitivity using cell suspension or organoids has shown a strong correlation with clinical responses. Furthermore, organoids matched the original tumor histology and microenvironment to a satisfactory degree. Establishment of xenografts proved feasible in the majority of patients; the technique could also preserve the tumor architecture and displayed high physiological relevance to the clinical situation.Conclusions: Although a major clinical study directly comparing conventional chemotherapy to personalized treatment guided by functional assays is yet to be published, this approach has gained popularity given the low efficacy of personalized medicine based on genetic alterations. The results thus far show promise for a better outcome for patients with metastatic STS.
背景/目的：软组织肉瘤（STSs）是起源于间叶组织的罕见肿瘤，包含100多种具有不同生物学行为、转移模式和治疗反应的组织学亚型。尽管多模式治疗取得进展，转移性STS患者的总生存率仍然较差，主要归因于对基于多柔比星和异环磷酰胺的传统化疗反应较弱。方法：本综述探讨了从传统"一刀切"治疗向个体化医疗策略的演变，主要聚焦于基于患者来源肿瘤样本的检测方法，并强调其在指导STS个体化治疗决策和改善临床结局方面日益重要的作用。与依赖高通量技术（如全基因组测序）识别可靶向基因组改变的其他个体化疗法相比，这些被称为功能性精准肿瘤学的方法更接近临床实际情况，而前者迄今未能在STS治疗中显示出令人信服的反应。结果：已在STS患者中测试的主要功能性精准肿瘤学平台包括体外细胞活力测试、类器官培养和患者来源异种移植模型。每种方法均具有优势和局限性。在此背景下，使用细胞悬液或类器官进行的体外药物敏感性测试已显示出与临床反应的高度相关性。此外，类器官在相当程度上匹配了原始肿瘤的组织学和微环境特征。异种移植模型的建立被证明在大多数患者中可行；该技术还能保留肿瘤结构，并显示出与临床情况高度相关的生理学意义。结论：尽管直接比较传统化疗与功能性检测指导的个体化治疗的大型临床研究尚未发表，但鉴于基于基因改变的个体化医疗疗效有限，该方法已获得广泛关注。迄今为止的结果显示，该方法有望为转移性STS患者带来更好的治疗结局。
Functional Assays to Guide Personalized Oncological Treatment of Patients with Soft-Tissue Sarcomas
肿瘤(癌症)患者之家