Ricci F, Carrassa L, Christodoulou M S, Passarella D, Michel B, Benhida R, Martinet N, Hunyadi A, Ioannou E, Roussis V, Musso L, Dallavalle S, Silvestri R, Westwood N, Mori M, Ingallina C, Botta B, Kavetsou E, Detsi A, Majer Z, Hudecz F, Bosze S, Kaminska B, Hansen T V, Bertrand P, Athanassopoulos C M, Damia G
IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156 Milan, Italy.
Dipartimento di Chimica - Universita degli Studi di Milano - Via C. Golgi 19, 20133 Milan, Italy.
Comb Chem High Throughput Screen. 2018;21(1):50-56. doi: 10.2174/1386207321666180124093406.
Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of "cancer stem cells" could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy.
We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them.
Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.
上皮性卵巢癌预后较差，主要原因是其诊断较晚以及在首个铂类方案治疗后出现耐药。特定“癌症干细胞”群体的存在可能导致肿瘤复发和对治疗产生耐药。因此，特异性靶向这一肿瘤细胞亚群对于提高治疗反应至关重要。
我们筛选了在COST CM1106行动期间组装的化合物库，以寻找对卵巢干细胞有活性的化合物类别。我们在此报告在两种卵巢癌干细胞及其衍生的分化细胞中进行的高通量筛选试验结果。
有趣的是，存在仅对干细胞有活性、仅对分化细胞有活性以及对两种细胞群体都有活性的化合物。即使这些数据需要在专门的剂量反应细胞毒性实验中进行验证，但对化合物结构的持续分析将为机制性药物研究开辟道路，以选择能够改善卵巢癌患者预后的化合物。
