ArticleJournal of molecular medicine (Berlin, Germany)2018
The combination of everolimus and terameprocol exerts synergistic antiproliferative effects in endometrial cancer: molecular role of insulin-like growth factor binding protein 2.
Article in Journal of molecular medicine (Berlin, Germany), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Prognostic value of IGFBP2 in various cancers: a systematic review and meta-analysis.Cancer medicine · 2022Pooled it
- Dual PI3K/AKT/mTOR and CDK4/6 inhibition suppresses survivin to overcome uterine dedifferentiated endometrial carcinoma.Cancer gene therapy · 2026Article
- Combined targeting poly (ADP-ribose) polymerase and receptor tyrosine kinase inhibits ovarian clear cell carcinoma progression through disrupted ribosome biogenesis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- IGFBP2 Promotes Proliferation and Glycolysis of Endometrial Cancer by Regulating PKM2/HIF-1α Axis.Cancer science · 2025Article
- AKT inhibitors in gynecologic oncology: past, present and future.Frontiers in oncology · 2025Review
- Targeting the inhibitors of apoptosis proteins (IAPs) to combat drug resistance in cancers.Frontiers in pharmacology · 2025Review
- A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR).Cell reports. Medicine · 2024Article
- Combining MTI-31 with RAD001 inhibits tumor growth and invasion of kidney cancer by activating autophagy.Journal of applied genetics · 2024Article
- Small Molecule Inhibitors Targeting the "Undruggable" Survivin: The Past, Present, and Future from a Medicinal Chemist's Perspective.Journal of medicinal chemistry · 2023Review
- Survivin Small Molecules Inhibitors: Recent Advances and Challenges.Molecules (Basel, Switzerland) · 2023Review
- Article
- Inhibition of BIRC2 Sensitizes α7-HPV-Related Cervical Squamous Cell Carcinoma to Chemotherapy.International journal of molecular sciences · 2021Article
- Nucleophosmin/B23 promotes endometrial cancer cell escape from macrophage phagocytosis by increasing CD24 expression.Journal of molecular medicine (Berlin, Germany) · 2021Article
- RAD001 targeted HUVECs reverses 12-lipoxygenase-induced angiogenesis in oesophageal squamous cell carcinoma.Journal of cellular and molecular medicine · 2021Article
- Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer.Methods and protocols · 2020Article
- Synergistic effects of pazopanib and hyperthermia against uterine leiomyosarcoma growth mediated by downregulation of histone acetyltransferase 1.Journal of molecular medicine (Berlin, Germany) · 2020Article
- The Prognostic Values of the Insulin-Like Growth Factor Binding Protein Family in Ovarian Cancer.BioMed research international · 2020Article
- Palbociclib Promotes Dephosphorylation of NPM/B23 at Threonine 199 and Inhibits Endometrial Cancer Cell Growth.Cancers · 2019Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic PIK3CA mutations are common in endometrial cancers, and the PI3K/AKT/mTOR pathway is targetable by drugs. We sought to investigate whether the combination of an mTOR inhibitor, everolimus (RAD001), and an AKT inhibitor, terameprocol (M4N), exerts better antiproliferative effects in endometrial cancer. The molecular mechanisms underlying their pharmacological action were also examined. The combination of RAD001 and M4N exerted in vitro synergistic effects on cell viability, apoptosis, and expression of IGFBP2 in endometrial cancer cells. Mechanistically, the Sp1 site on the IGFBP2 promoter was required for RAD001- and M4N-induced downregulation. IGFBP2 protein expression was higher in endometrial cancer than in the normal endometrium (P < 0.001). Furthermore, elevated IGFBP2 histoscores were significantly associated with a lower overall survival (P = 0.021). In conclusion, our in vitro results demonstrate that RAD001 and M4N exert synergistic antiproliferative effects against endometrial cancer cells, which appeared to be mediated by the inhibition of IGFBP2, a key anti-apoptotic regulator. Further clinical studies of this drug combination in patients with endometrial cancer may be warranted, especially in the presence of PIK3CA and IGFBP2 aberrations. KEY MESSAGES: RAD001 and M4N synergistically suppress endometrial cancer growth. IGFBP2 is overexpressed in endometrial cancer. The combination of RAD001 and M4N significantly reduces IGFBP2 overexpression. Sp1 binding site on the IGFBP2 promoter is required for RAD001- and M4N-induced downregulation. High IGFBP2 histoscore in endometrial cancer portends a poor prognosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.