Angiosarcoma is a rare subtype of malignant neoplasm originating from vascular or lymphatic endothelial cells; its low incidence has posed significant challenges for comprehensive investigations into its pathogenic mechanisms and the development of innovative treatment modalities through in vitro and in vivo models. Recent endeavors spearheaded by patient-partnered research initiatives have aimed to elucidate the intricacies of angiosarcomas by leveraging biological omics approaches, with the overarching objective of enhancing prognostic indicators and therapeutic options for this uncommon pathology. To bridge the gap between preclinical research and translational applications, we engineered angiosarcoma-derived organoids from surgically resected primary tumors, hereafter referred to as “sarconoids,” as a proof-of-concept model. A novel protocol for the establishment of these sarconoids has been developed and validated. To ensure that the sarconoids faithfully recapitulate the heterogeneity and complexities of the patients’ original tumors, including transcriptomic signatures, cell-type specificity, and morphological traits, exhaustive histological and transcriptomic analyses were conducted. Subsequently, we expanded the scope of our study to include an evaluation of a sarconoid-based drug screening platform; for this purpose, a drug library (AOD IX), supplied by the National Cancer Institute’s Developmental Therapeutics Program, was screened using 96-well plates. Our findings suggest that sarconoids can be reliably generated from angiosarcoma patient-derived tissues and can serve as accurate models for evaluating therapeutic responses, thereby holding far-reaching implications for translational research and clinical applications aimed at advancing our understanding and treatment of angiosarcoma.

中文翻译：

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从血管肉瘤患者产生肌素作为一种基于系统的合理治疗方法


血管肉瘤是一种罕见的恶性肿瘤亚型，起源于血管或淋巴内皮细胞;其低发病率为全面研究其致病机制和通过体外和体内模型开发创新治疗方式带来了重大挑战。由患者合作研究计划牵头的最新努力旨在通过利用生物组学方法阐明血管肉瘤的复杂性，其总体目标是增强这种罕见病理的预后指标和治疗选择。为了弥合临床前研究和转化应用之间的差距，我们从手术切除的原发性肿瘤中设计了血管肉瘤衍生的类器官，以下简称“类肉瘤”，作为概念验证模型。已经开发并验证了一种用于建立这些类肌瘤的新方案。为了确保类肌瘤忠实地概括患者原始肿瘤的异质性和复杂性，包括转录组特征、细胞类型特异性和形态学特征，进行了详尽的组织学和转录组学分析。随后，我们扩大了研究范围，包括对基于肌激素的药物筛选平台的评估;为此，使用 96 孔板筛选了由美国国家癌症研究所发育治疗学计划提供的药物库 （AOD IX）。 我们的研究结果表明，肌瘤可以从血管肉瘤患者来源的组织可靠地产生，并且可以作为评估治疗反应的准确模型，从而对旨在促进我们对血管肉瘤的理解和治疗的转化研究和临床应用具有深远的影响。