Background: Tumors of the pleura, such as metastatic lung cancer and mesothelioma, are amongst the most lethal and therapy-resistant tumors. The first manifestation of the disease is often pleural effusion, the first available material for diagnosis. The five-year survival rate is exceptionally low, around 10–20%, and only a small proportion of patients harbor mutations that allow targeted treatments. Almost all patients develop resistance to treatment, which is often palliative. There is therefore an urgent need to refine the selection of drugs and patients for personalized treatment. Methods: We isolated and cultured cells from pleural effusions in 3D cell aggregates and compared their drug sensitivity ex vivo to the clinical response to the same chemotherapeutic agents, combined with targeted sequencing and network analysis. Results: The ex vivo drug response showed a positive correlation with the treatment response and survival of patients in the clinic, with a stronger link to overall survival than to progression-free survival. Cryopreserved cells showed a similar response to freshly collected cells from the clinic. Conclusions: The findings advance the field of ex vivo screening and present an opportunity to combine strategies for functional precision medicine with comprehensive characterization of disease for improved treatment and future management of lung cancer.
背景：胸膜肿瘤，如转移性肺癌和间皮瘤，属于最具致命性和治疗抵抗性的肿瘤之一。该疾病的首发表现常为胸腔积液，这也是诊断中最早可获取的材料。其五年生存率极低，约为10%至20%，且仅有少数患者携带可进行靶向治疗的突变。几乎所有患者最终都会对治疗产生耐药性，而现有治疗多为姑息性手段。因此，亟需优化药物与患者的选择以实现个体化治疗。方法：我们从胸腔积液中分离细胞并进行三维细胞聚集体培养，通过体外药物敏感性测试，结合靶向测序与网络分析，将其与患者对相同化疗药物的临床反应进行对比。结果：体外药物反应与患者的临床治疗反应及生存期呈正相关，且与总生存期的关联性较无进展生存期更为显著。冷冻保存的细胞与临床新鲜采集的细胞表现出相似的反应特性。结论：本研究推进了体外筛选领域的发展，为整合功能性精准医学策略与疾病全面表征提供了契机，有望改善肺癌治疗及未来管理策略。
肿瘤(癌症)患者之家