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利用患者来源细胞培养物上的免疫测定法将非小细胞肺癌患者的反应与药物敏感性相关联。

Associating Patient Responses with Drug Sensitivity in Non-Small Cell Lung Carcinoma Using an Immunoassay on Patient-Derived Cell Cultures.

作者信息

Podolski-Renić Ana, Jovanović Stojanov Sofija, Marić Dragana, Dinić Jelena, Dragoj Miodrag, Stepanović Ana, Lupšić Ema, Pajović Milica, Glumac Sofija, Ercegovac Maja, Pešić Milica

机构信息

Department of Neurobiology, Institute for Biological Research "Siniša Stanković"-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia.

School of Medicine, University of Belgrade, Dr. Subotića 8, 11000 Belgrade, Serbia.

出版信息

Curr Issues Mol Biol. 2025 Apr 17;47(4):281. doi: 10.3390/cimb47040281.

Abstract

: Non-small cell lung carcinoma (NSCLC) is characterized by its diverse molecular profiles and varying responses to treatment, highlighting the importance of precision medicine in optimizing therapeutic outcomes. A promising approach involves using patient-derived cellular models, which provide insights into the unique biology of individual tumors and their responsiveness to treatment. : We established short-term primary cell cultures from thirteen patients with NSCLC of different subtypes and stages, including both cancer and stromal cells. To evaluate the ex vivo cytotoxicity and selectivity of eight chemotherapeutics and erlotinib, we employed an immunoassay, and the results were analyzed using an automated imaging system. Scoring of the obtained results was also performed. The ex vivo responses to cisplatin, etoposide, and paclitaxel were correlated with the patients' responses to therapy. We used Kaplan-Meier analysis to assess progression-free survival (PFS) differences among patient groups. : NSCLC cells exhibited significant variability in their responses to drugs, with stromal cells demonstrating greater sensitivity. Tumors at stages I-III responded to multiple treatments, whereas stage IV cells showed considerable resistance. Erlotinib effectively reduced cancer cell growth at lower doses but plateaued at higher concentrations. The immunoassay indicated 67% sensitivity and 100% specificity in predicting patient responses to chemotherapy. Sensitivity to etoposide and paclitaxel correlated with progression-free survival (PFS). A personalized treatment strategy, such as our immunoassay based on the ex vivo responses of cancer patients' cells, can guide treatment decisions and, in some cases, serve as surrogate biomarkers for tumor types that lack actionable biomarkers.

摘要

非小细胞肺癌(NSCLC)具有多样的分子特征和对治疗的不同反应,这凸显了精准医学在优化治疗效果方面的重要性。一种有前景的方法是使用患者来源的细胞模型,该模型能深入了解个体肿瘤的独特生物学特性及其对治疗的反应。

我们从13例不同亚型和分期的NSCLC患者中建立了短期原代细胞培养物,包括癌细胞和基质细胞。为了评估8种化疗药物和厄洛替尼的体外细胞毒性和选择性,我们采用了免疫测定法,并使用自动成像系统分析结果。还对所得结果进行了评分。对顺铂、依托泊苷和紫杉醇的体外反应与患者的治疗反应相关。我们使用Kaplan-Meier分析来评估患者组之间的无进展生存期(PFS)差异。

NSCLC细胞对药物的反应表现出显著差异,基质细胞显示出更高的敏感性。I - III期肿瘤对多种治疗有反应,而IV期细胞则表现出相当的抗性。厄洛替尼在较低剂量时能有效降低癌细胞生长,但在较高浓度时趋于平稳。免疫测定法在预测患者对化疗的反应中显示出67%的敏感性和100%的特异性。对依托泊苷和紫杉醇的敏感性与无进展生存期(PFS)相关。一种个性化的治疗策略,例如基于癌症患者细胞体外反应的我们的免疫测定法,可以指导治疗决策,并且在某些情况下,可作为缺乏可操作生物标志物的肿瘤类型的替代生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c5/12026358/f08a2d0f392c/cimb-47-00281-g001.jpg

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