Small Molecules Identified from a Quantitative Drug Combinational Screen Resensitize Cisplatin's Response in Drug-Resistant Ovarian Cancer Cells.

Small Molecules Identified from a Quantitative Drug Combinational Screen Resensitize Cisplatin's Response in Drug-Resistant Ovarian Cancer Cells. Transl Oncol. 2018 Jul 04;11(4):1053-1064 Authors: Sima N, Sun W, Gorshkov K, Shen M, Huang W, Zhu W, Xie X, Zheng W, Cheng X Abstract Drug resistance to chemotherapy occurs in many ovarian cancer patients resulting in failure of treatment. Exploration of drug resistance mechanisms and identification of new therapeutics that overcome the drug resistance can improve patient prognosis. Following a quantitative combination screen of 6060 approved drugs and bioactive compounds in a cisplatin-resistant A2780-cis ovarian cancer cell line, 38 active compounds with IC50s under 1 μM suppressed the growth of cisplatin-resistant ovarian cancer cells. Among these confirmed compounds, CUDC-101, OSU-03012, oligomycin A, VE-821, or Torin2 in a combination with cisplatin restored cisplatin's apoptotic response in the A2780-cis cells, while SR-3306, GSK-923295, SNX-5422, AT-13387, and PF-05212384 directly suppressed the growth of A2780-cis cells. One of the mechanisms for overcoming cisplatin resistance in these cells is mediated by the inhibition of epidermal growth factor receptor (EGFR), though not all the EGFR inhibitors are equally active. The increased levels of total EGFR and phosphorylated-EGFR (p-EGFR) in the A2780-cis cells were reduced after the combined treatment of cisplatin with EGFR inhibito...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Tags: Transl Oncol Source Type: research