ArticleScientific reports2019
Evaluation of the dual mTOR/PI3K inhibitors Gedatolisib (PF-05212384) and PF-04691502 against ovarian cancer xenograft models.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
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- Future investigative directions for novel therapeutic targets in head and neck cancer.Expert review of anticancer therapy · 2024Review
- Article
- Gedatolisib shows superior potency and efficacy versus single-node PI3K/AKT/mTOR inhibitors in breast cancer models.NPJ breast cancer · 2024Article
- Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response.Cancer cell international · 2024Article
- Optimization of mTOR Inhibitors Using Property-Based Drug Design and Free-Wilson Analysis for Improved In Vivo Efficacy.ACS medicinal chemistry letters · 2023Article
- Molecular Profile of Canine Hemangiosarcoma and Potential Novel Therapeutic Targets.Veterinary sciences · 2023Review
- Review
- Selective Eradication of Colon Cancer Cells Harboring PI3K and/or MAPK Pathway Mutations in 3D Culture by Combined PI3K/AKT/mTOR Pathway and MEK Inhibition.International journal of molecular sciences · 2023Article
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Insights into the roles and driving forces of CCT3 in human tumors.Frontiers in pharmacology · 2022Article
- Recent Advances in Dual PI3K/mTOR Inhibitors for Tumour Treatment.Frontiers in pharmacology · 2022Review
- Article
- Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence.Journal of clinical medicine · 2020Review
- Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection.Pharmaceuticals (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study investigated the antitumour effects of two dual mTOR/PI3K inhibitors, gedatolisib (WYE-129587/PKI-587/PF-05212384) and PF-04691502 against a panel of six human patient derived ovarian cancer xenograft models. Both dual mTOR/PI3K inhibitors demonstrated antitumour activity against all xenografts tested. The compounds produced tumour stasis during the treatment period and upon cessation of treatment, tumours re-grew. In several models, there was an initial rapid reduction of tumour volume over the first week of treatment before tumour stasis. No toxicity was observed during treatment. Biomarker studies were conducted in two xenograft models; phospho-S6 (Ser235/236) expression (as a readout of mTOR activity) was reduced over the treatment period in the responding xenograft but expression increased to control (no treatment) levels on cessation of treatment. Phospho-AKT (Ser473) expression (as a readout of PI3K) was inhibited by both drugs but less markedly so than phospho-S6 expression. Initial tumour volume reduction on treatment and regrowth rate after treatment cessation was associated with phospho-S6/total S6 expression ratio. Both drugs produced apoptosis but minimally influenced markers of proliferation (Ki67, phospho-histone H3). These results indicate that mTOR/PI3K inhibition can produce broad spectrum tumour growth stasis in ovarian cancer xenograft models during continuous chronic treatment and this is associated with apoptosis.
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