Varbanov Hristo P, Kuttler Fabien, Banfi Damiano, Turcatti Gerardo, Dyson Paul J
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Biomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
PLoS One. 2017 Feb 6;12(2):e0171052. doi: 10.1371/journal.pone.0171052. eCollection 2017.
Advances in treatment strategies together with an earlier diagnosis have considerably increased the average survival of cancer patients over the last four decades. Nevertheless, despite the growing number of new antineoplastic agents introduced each year, there is still no adequate therapy for problematic malignancies such as pancreatic, lung and stomach cancers. Consequently, it is important to ensure that existing drugs used to treat other types of cancers, and potentially other diseases, are not overlooked when searching for new chemotherapy regimens for these problematic cancer types. We describe a screening approach that identifies chemotherapeutics for the treatment of lung and pancreatic cancers, based on drugs already approved for other applications. Initially, the 1280 chemically and pharmacologically diverse compounds from the Prestwick Chemical Library® (PCL) were screened against A549 (lung cancer) and PANC-1 (pancreatic carcinoma) cells using the PrestoBlue fluorescent-based cell viability assay. More than 100 compounds from the PCL were identified as hits in one or both cell lines (80 of them, being drugs used to treat diseases other than cancer). Selected PCL hits were further evaluated in a dose-response manner. Promising candidates for repositioning emanating from this study include antiparasitics, cardiac glycosides, as well as the anticancer drugs vorinostat and topotecan.
在过去的四十年中，治疗策略的进步以及早期诊断显著提高了癌症患者的平均生存期。然而，尽管每年引入的新型抗肿瘤药物数量不断增加，但对于胰腺癌、肺癌和胃癌等难治性恶性肿瘤仍没有足够的治疗方法。因此，在为这些难治性癌症类型寻找新的化疗方案时，确保不忽视用于治疗其他类型癌症以及潜在其他疾病的现有药物非常重要。我们描述了一种筛选方法，该方法基于已被批准用于其他用途的药物，来鉴定用于治疗肺癌和胰腺癌的化学治疗药物。最初，使用基于PrestoBlue荧光的细胞活力测定法，针对A549（肺癌）和PANC-1（胰腺癌）细胞对来自Prestwick化学文库®（PCL）的1280种化学和药理性质各异的化合物进行了筛选。PCL中的100多种化合物在一种或两种细胞系中被鉴定为有效命中物（其中80种是用于治疗癌症以外疾病的药物）。对选定的PCL有效命中物进行了剂量反应方式的进一步评估。这项研究中有望重新定位的候选药物包括抗寄生虫药、强心苷以及抗癌药物伏立诺他和拓扑替康。
