Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
Cell Stem Cell. 2024 Oct 3;31(10):1524-1542.e4. doi: 10.1016/j.stem.2024.08.010. Epub 2024 Sep 20.
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.
肉瘤是一种罕见的恶性肿瘤，具有超过 100 种不同的组织学亚型。其罕见性和异质性给确定有效治疗方法带来了巨大挑战，而已批准的治疗方案显示出不同的反应。需要新型的、个性化的治疗方法来改善患者的预后。患者来源的肿瘤类器官（PDTO）可以模拟多种恶性肿瘤的肿瘤行为。我们利用 PDTO 来描述肉瘤中耐药性和敏感性的情况，从 24 种不同的肉瘤亚型中收集了 126 名患者的 194 个样本。我们的高通量类器官筛选流水线测试了单一药物和联合用药，从手术到获得结果只需要一周的时间。药物敏感性与肿瘤亚型、治疗史和疾病进程等临床特征相关。PDTO 筛选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 推荐的有效治疗方案，这表明我们的流水线有潜力提供可行的治疗信息。
