ArticleOncotarget2016
Synergistic antitumor effects of combination PI3K/mTOR and MEK inhibition (SAR245409 and pimasertib) in mucinous ovarian carcinoma cells by fluorescence resonance energy transfer imaging.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor.Gynecologic oncology · 2019Trial
- Review
- Mucinous Ovarian Carcinoma: Integrating Molecular Stratification into Surgical and Therapeutic Management.Biomedicines · 2025Review
- Review
- Role of RAS signaling in ovarian cancer.F1000Research · 2022Review
- Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas.Cancers · 2021Review
- Targeting the PI3K/AKT/mTOR Signaling Pathway in Lung Cancer: An Update Regarding Potential Drugs and Natural Products.Molecules (Basel, Switzerland) · 2021Review
- Cellular Mechanism of Gene Mutations and Potential Therapeutic Targets in Ovarian Cancer.Cancer management and research · 2021Review
- P53 and PIK3CA Mutations in KRAS/HER2 Negative Ovarian Intestinal-Type Mucinous Carcinoma Associated with Mature Teratoma.Case reports in obstetrics and gynecology · 2020Article
- Kaempferol, a natural dietary flavonoid, suppresses 17β-estradiol-induced survivin expression and causes apoptotic cell death in endometrial cancer.Oncology letters · 2018Article
- Pharmacology of Pimasertib, A Selective MEK1/2 Inhibitor.European journal of drug metabolism and pharmacokinetics · 2018Review
- Recent Insights into Mucinous Ovarian Carcinoma.International journal of molecular sciences · 2018Review
- Differential compensation mechanisms define resistance to PI3K inhibitors inOtorhinolaryngology-head and neck surgery · 2016Article
- An open-label, single-arm, phase II trial of buparlisib in patients with melanoma brain metastases not eligible for surgery or radiosurgery-the BUMPER study.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study was to clarify the synergistic effects of dual inhibition of the PI3K/mTOR and MAPK pathways in ovarian mucinous carcinoma (OMC) cells, using fluorescence resonance energy transfer (FRET) imaging. We exposed 6 OMC cell lines to a PI3K/mTOR inhibitor (voxtalisib, SAR245409) and/or a MEK inhibitor (pimasertib), and evaluated synergistic effects using the Chou-Talalay method. Then, S6K (PI3K pathway) and ERK (MAPK pathway) kinase activities, and their individual proliferative or cytotoxic effects were calculated by time-lapse FRET imaging. In combination with SAR245409, pimasertib (30 nM) synergistically inhibited cell growth (combination indexes: 0.03-0.5) and induced apoptosis in all 6 OMC cell lines. FRET-imaging results demonstrated that ERK inhibition induced both anti-proliferation and apoptosis in a dose-dependent manner in both MCAS and OAW42 cells. However, S6K inhibition suppressed proliferation in a threshold manner in both cell lines, although apoptosis was only induced in OAW42 cells. These results demonstrated that combined PI3K/mTOR and MEK inhibition exhibited synergistic antitumor effects in OMC cells and that FRET imaging is useful for analyzing kinase activities in live cells and elucidating their cytostatic and cytotoxic effects.
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