@article{cb45c5e651434c9e94ed0e26e41fb52f,
title = "Response Predictive Markers and Synergistic Agents for Drug Repositioning of Statins in Ovarian Cancer",
abstract = "In the field of drug repurposing, the use of statins for treating dyslipidemia is considered promising in ovarian cancer treatment based on epidemiological studies and basic research findings. Biomarkers should be established to identify patients who will respond to statin treatment to achieve clinical application. In the present study, we demonstrated that statins have a multifaceted mode of action in ovarian cancer and involve pathways other than protein prenylation. To identify biomarkers that predict the response to statins, we subjected ovarian cancer cells to microarray analysis and calculated Pearson{\textquoteright}s correlation coefficients between gene expression and cell survival after statin treatment. The results showed that VDAC1 and LDLRAP1 were positively and negatively correlated with the response to statins, respectively. Histoculture drug response assays revealed that statins were effective in clinical samples. We also confirmed the synergistic effects of statins with paclitaxel and panobinostat and determined that statins are hematologically safe to administer to statin-treated mice. Future clinical trials based on the expression of the biomarkers identified in this study for repurposing statins for ovarian cancer treatment are warranted.",
keywords = "Drug repurposing, LDLRAP1, Ovarian cancer, Statin, VDAC1",
author = "Yusuke Kobayashi and Takashi Takeda and Haruko Kunitomi and Fumiko Chiwaki and Masayuki Komatsu and Shimpei Nagai and Yuya Nogami and Kosuke Tsuji and Kenta Masuda and Hideaki Ogiwara and Hiroki Sasaki and Kouji Banno and Daisuke Aoki",
note = "Funding Information: Funding: This work was supported by KAKENHI (Japan Society for the Promotion of Science, Grant-in-aid; 20K09652, 21K15576), the National Institute of Biomedical Innovation (Program ID10-41), the National Cancer Center Research and Development Fund (28-A-11, 29-A-2, and 2020-J-2), and AMED (Japan Agency for Medical Research and Development) under Grant Number JP19ak0101043. Funding Information: This work was supported by KAKENHI (Japan Society for the Promotion of Science, Grant-in-aid; 20K09652, 21K15576), the National Institute of Biomedical Innovation (Program ID10-41), the National Cancer Center Research and Development Fund (28-A-11, 29-A-2, and 2020-J-2), and AMED (Japan Agency for Medical Research and Development) under Grant Number JP19ak0101043. The authors would like to acknowledge Tian-Li Wang and Ie-Ming Shih for the animal study at the Department of Pathology, School of Medicine, Johns Hopkins University. The authors sincerely thank Kayoko Kobori for fundamental support. The authors are grateful to Takeda Pharmaceutical Company for Takeda Research Support. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
month = feb,
doi = "10.3390/ph15020124",
language = "English",
volume = "15",
journal = "Pharmaceuticals",
issn = "1424-8247",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "2",
}
