文章：

患者来源肺癌细胞的药物反应预测靶向治疗的临床疗效

Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy

原文发布日期：14 February 2024

DOI: 10.3390/cancers16040778

类型: Article

开放获取: 是

英文摘要：

Intratumor heterogeneity leads to different responses to targeted therapies, even within patients whose tumors harbor identical driver oncogenes. This study examined clinical outcomes according to a patient-derived cell (PDC)-based drug sensitivity test in lung cancer patients treated with targeted therapies. From 487 lung cancers, 397 PDCs were established with a success rate of 82%. In 139 PDCs from advanced non-small-cell lung cancer (NSCLC) patients receiving targeted therapies, the standardized area under the curve (AUC) values for the drugs was significantly correlated with their tumor response (p= 0.002). Among 59 chemo-naive EGFR/ALK-positive NSCLC patients, the PDC non-responders showed a significantly inferior response rate (RR) and progression-free survival (PFS) for the targeted drugs than the PDC responders (RR, 25% vs. 78%,p= 0.011; median PFS, 3.4 months [95% confidence interval (CI), 2.8–4.1] vs. 11.8 months [95% CI, 6.5–17.0],p< 0.001). Of 25 EGFR-positive NSCLC patients re-challenged with EGFR inhibitors, the PDC responder showed a higher RR than the PDC non-responder (42% vs. 15%). Four patients with wild-type EGFR or uncommon EGFR-mutant NSCLC were treated with EGFR inhibitors based on their favorable PDC response to EGFR inhibitors, and two patients showed dramatic responses. Therefore, the PDC-based drug sensitivity test results were significantly associated with clinical outcomes in patients with EGFR- or ALK-positive NSCLC. It may be helpful for predicting individual heterogenous clinical outcomes beyond genomic alterations.

摘要翻译： 

肿瘤内异质性导致对靶向治疗的不同反应，即使是在携带相同驱动癌基因的患者中也是如此。本研究基于患者来源细胞（PDC）药物敏感性测试，分析了接受靶向治疗的肺癌患者的临床结局。从487例肺癌样本中成功建立了397个PDC，成功率为82%。在139例接受靶向治疗的晚期非小细胞肺癌（NSCLC）患者的PDC中，药物的标准化曲线下面积（AUC）值与肿瘤反应显著相关（p=0.002）。在59例未接受过化疗的EGFR/ALK阳性NSCLC患者中，PDC无应答者对靶向药物的应答率（RR）和无进展生存期（PFS）均显著低于PDC应答者（RR：25% vs. 78%，p=0.011；中位PFS：3.4个月[95%置信区间（CI），2.8–4.1] vs. 11.8个月[95% CI，6.5–17.0]，p<0.001）。在25例再次接受EGFR抑制剂治疗的EGFR阳性NSCLC患者中，PDC应答者的RR高于PDC无应答者（42% vs. 15%）。4例野生型EGFR或罕见EGFR突变NSCLC患者基于其PDC对EGFR抑制剂良好的反应性接受了EGFR抑制剂治疗，其中2例患者显示出显著疗效。因此，基于PDC的药物敏感性测试结果与EGFR或ALK阳性NSCLC患者的临床结局显著相关。该方法可能有助于预测超越基因组改变的个体异质性临床结局。

原文链接：

Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy