Wu Ming, Hong Guodai, Chen Yu, Ye Lina, Zhang Kang, Cai Kaihong, Yang Huadong, Long Xiang, Gao Wenbin, Li Hui
Wuhan University Shenzhen Institute, Shenzhen, Guangdong, China.
Shenzhen Luohu People's Hospital, Shenzhen, Guangdong, China.
J Int Med Res. 2020 Sep;48(9):300060520955058. doi: 10.1177/0300060520955058.
Patients with non-small-cell lung cancer (NSCLC) and primary or acquired resistance do not respond to targeted drugs. We explored whether cancer cells can be cultured from liquid biopsies from patients with primary resistance to tyrosine kinase inhibitors (TKIs). We aimed to predict patients' responses to drugs according to drug testing results.
Cancer cell cultures were established from the pleural effusion of a patient with TKI-resistant NSCLC using a conditional reprogramming technique. Phenotypic drug sensitivity tests were performed using the Cell Counting Kit-8 assay. We tested individual drugs and compared the synergistic and inhibitory effects of drug combinations.
The results of our sensitivity test using the combination of cisplatin and pemetrexed were correlated with the patient's response.
This represents the first successful report of predictive testing for combination therapy in patients with epidermal growth factor receptor-mutant NSCLC and primary TKI resistance. This strategy should be applicable to both chemotherapies and targeted therapies, and it will significantly improve the clinical treatment and management of patients with NSCLC and primary or acquired resistance to targeted therapies, as well as patients lacking targetable mutations.
非小细胞肺癌(NSCLC)患者以及存在原发性或获得性耐药的患者对靶向药物无反应。我们探究了能否从对酪氨酸激酶抑制剂(TKIs)产生原发性耐药的患者的液体活检样本中培养癌细胞。我们旨在根据药物检测结果预测患者对药物的反应。
使用条件重编程技术,从一名对TKI耐药的NSCLC患者的胸腔积液中建立癌细胞培养物。使用细胞计数试剂盒-8检测法进行表型药物敏感性测试。我们测试了单一药物,并比较了药物组合的协同和抑制作用。
我们使用顺铂和培美曲塞联合用药的敏感性测试结果与患者的反应相关。
这是表皮生长因子受体突变的NSCLC和原发性TKI耐药患者联合治疗预测性检测的首个成功报告。该策略应适用于化疗和靶向治疗,并且将显著改善NSCLC以及对靶向治疗存在原发性或获得性耐药的患者,以及缺乏可靶向突变的患者的临床治疗与管理。