Response Predictive Markers and Synergistic Agents for Drug Repositioning of Statins in Ovarian Cancer

Yusuke Kobayashi, Takashi Takeda, Haruko Kunitomi, Fumiko Chiwaki, Masayuki Komatsu, Shimpei Nagai, Yuya Nogami, Kosuke Tsuji, Kenta Masuda, Hideaki Ogiwara, Hiroki Sasaki, Kouji Banno, Daisuke Aoki

Research output: Contribution to journalArticlepeer-review

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’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.

Original languageEnglish
Article number124
JournalPharmaceuticals
Volume15
Issue number2
DOIs
Publication statusPublished - 2022 Feb
Externally publishedYes

Keywords

  • Drug repurposing
  • LDLRAP1
  • Ovarian cancer
  • Statin
  • VDAC1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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