Sarcomas are rare malignancies with over 100 distinct histological subtypes. Their rarity and heterogeneity pose significant challenges to identifying effective therapies, and approved regimens show varied responses. Novel, personalized approaches to therapy are needed to improve patient outcomes. Patient-derived tumor organoids (PDTOs) model tumor behavior across an array of malignancies. We leverage PDTOs to characterize the landscape of drug resistance and sensitivity in sarcoma, collecting 194 specimens from 126 patients spanning 24 distinct sarcoma subtypes. Our high-throughput organoid screening pipeline tested single agents and combinations, with results available within a week from surgery. Drug sensitivity correlated with clinical features such as tumor subtype, treatment history, and disease trajectory. PDTO screening can facilitate optimal drug selection and mirror patient outcomes in sarcoma. We could identify at least one FDA-approved or NCCN-recommended effective regimen for 59% of the specimens, demonstrating the potential of our pipeline to provide actionable treatment information.

中文翻译：

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肉瘤的药物敏感性和耐药性概况


肉瘤是罕见的恶性肿瘤，有 100 多种不同的组织学亚型。它们的稀有性和异质性对确定有效的治疗方法提出了重大挑战，并且批准的治疗方案显示出不同的反应。需要新颖、个性化的治疗方法来改善患者的治疗效果。患者来源的肿瘤类器官 (PDTO) 可模拟一系列恶性肿瘤的肿瘤行为。我们利用 PDTO 来表征肉瘤的耐药性和敏感性，收集了来自 126 名患者的 194 份标本，涵盖 24 种不同的肉瘤亚型。我们的高通量类器官筛选流程测试了单一药物和组合，并在手术后一周内得出结果。药物敏感性与肿瘤亚型、治疗史和疾病轨迹等临床特征相关。 PDTO 筛查可以促进最佳药物选择并反映肉瘤患者的治疗结果。我们可以为 59% 的样本确定至少一种 FDA 批准或 NCCN 推荐的有效方案，这证明了我们的管道提供可操作的治疗信息的潜力。