PO.TB04.01 · 肿瘤生物学
绘制肿瘤异质性图谱：使用3D功能精准平台评估同期匹配的原发与转移肿瘤的离体药物反应
Mapping tumor heterogeneity: Ex-Vivo drug responses in synchronous matched primary and metastatic tumors using a 3D functional precision platform
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摘要 Abstract
中文摘要
背景：肿瘤异质性仍是治疗耐药的主要驱动因素，确定转移播散如何影响功能性药物反应对临床决策至关重要。我们已开发出一种3D微肿瘤功能分析检测方法，该方法可保留天然肿瘤结构，并能在CLIA实验室环境中于7至10天内生成可靠的药物反应谱。本次更新以额外的同期配对癌症标本扩充了我们早期的数据集。
方法：匹配的同期肿瘤取自原发卵巢癌、结肠癌和乳腺癌，其转移灶位于网膜、肝脏、腹膜、肺和腋窝。所有样本均经冷藏并隔夜运输，在24小时内处理，并暴露于NCCN推荐及机制相关的化疗或靶向治疗药物。72小时后评估细胞活力以生成细胞毒性剂量反应，并采用决定系数（R2）测量一致性。
结果：我们报告了来自7例具有匹配原发与转移肿瘤患者的162项药物比较。药物反应一致性因转移途径而有很大差异。局部转移显示出最高的相关性。淋巴源性转移（乳腺至腋窝）显示中等相关性。血源性转移的相关性最弱，其中结肠-肺以及卵巢软组织/结肠配对仅显示出中等程度的相似性。然而，有一例卵巢向网膜的局部扩散仅表现出中等偏强的相关性。
结论：数据提示，来自局部转移的敏感性和耐药性谱往往与原发肿瘤的谱有良好相关性。此外，对于淋巴源性或血源性扩散的转移，尽管相关性往往仅为中等，功能性分析或许仍有助于显著降低接受无效治疗的风险。
同期匹配肿瘤样本的相关性 肿瘤类型 转移部位 关系 R2 卵巢 网膜 局部 0.98 卵巢 肝包膜 局部 0.93 结肠 腹膜 局部 0.93 卵巢 网膜 局部 0.47 乳腺 腋窝 淋巴源性 0.77 结肠 肺 血源性 0.51 卵巢 软组织和结肠 血源性 0.42
查看英文原文 English abstract
Background : Tumor heterogeneity remains a major driver of therapeutic resistance and determining how metastatic dissemination affects functional drug response is critical for clinical decision making. We have developed a 3D microtumor functional profiling assay that preserves native tumor architecture and produces reliable drug response profiles within 7 to 10 days in a CLIA lab environment. This update expands our earlier dataset with additional synchronous pairs of cancer specimen.
Methods : Matched synchronous tumors were obtained from primary ovary, colon, and breast cancers with metastases into the omentum, liver, peritoneum, lung, and axilla. All samples were cooled and shipped overnight, processed within 24 hours, and exposed to NCCN recommended and mechanistically relevant chemo or targeted therapies. Viability was assessed after 72 h to generate cytotoxicity dose responses and concordance was measured using coefficient of determination (R2).
Results : We are reporting on 162 drug comparisons from seven patients with matched primary and metastatic tumors. Drug-response concordance varied substantially by metastatic route. Local metastases showed the highest correlation. A lymphogenic metastasis (breast to axilla) showed moderate correlation. Hematogenic metastases exhibited the weakest correlation, with colon-lung and ovarian soft-tissue/colon pairs showing only modest similarity. However, one ovarian local spread to the omentum demonstrated only moderately strong correlation.
Conclusions : The data suggest that sensitivity and resistance spectra from local metastases tend to correlate well with those from the primary tumors. Furthermore, for metastases from lymphogenic or hematogenic spread, while the correlation tends to be only modest, functional profiling may still be useful to significantly reduce the risk for receiving ineffective treatment.
Correlation of synchronously matched tumor samples Tumor Type Metastasis Relationship R 2 Ovarian Omentum Local 0.98 Ovarian Liver Capsule Local 0.93 Colon Peritoneum Local 0.93 Ovarian Omentum Local 0.47 Breast Axilla Lymphogenic 0.77 Colon Lung Hematogenic 0.51 Ovarian Soft Tissue and Colon Hematogenic 0.42
利益披露 Disclosure
R. Nitiyanandan,
Sagemedic Corp Employment, Stock Option.