ArticleAnti-cancer drugs2017
In-vitro and in-vivo combined effect of ARQ 092, an AKT inhibitor, with ARQ 087, a FGFR inhibitor.
Article in Anti-cancer drugs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
19 citing papers in PubMed, 28 citations in OpenAlex.
- ELF3 regulates epithelial-mesenchymal transition through TPM1 and promotes the development of endometrial cancer.Cytotechnology · 2025Article
- AKT inhibitors in gynecologic oncology: past, present and future.Frontiers in oncology · 2025Review
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- Vascular malformations: An overview of their molecular pathways, detection of mutational profiles and subsequent targets for drug therapy.Frontiers in neurology · 2023Review
- The onset of PI3K-related vascular malformations occurs during angiogenesis and is prevented by the AKT inhibitor miransertib.EMBO molecular medicine · 2022Article
- Article
- Inhibition of FGF-FGFR and VEGF-VEGFR signalling in cancer treatment.Cell proliferation · 2021Review
- The Evolving Role of FGFR2 Inhibitors in Intrahepatic Cholangiocarcinoma: From Molecular Biology to Clinical Targeting.Cancer management and research · 2021Review
- Potential relationship between Sirt3 and autophagy in ovarian cancer.Oncology letters · 2020Review
- SPR965, a Dual PI3K/mTOR Inhibitor, as a Targeted Therapy in Ovarian Cancer.Frontiers in oncology · 2020Article
- Bcl-2 inhibitors enhance FGFR inhibitor-induced mitochondrial-dependent cell death in FGFR2-mutant endometrial cancer.Molecular oncology · 2019Article
- Greensporone A, a Fungal Secondary Metabolite Suppressed Constitutively Activated AKT via ROS Generation and Induced Apoptosis in Leukemic Cell Lines.Biomolecules · 2019Article
- Fibroblast growth factor receptors as treatment targets in clinical oncology.Nature reviews. Clinical oncology · 2019Review
- Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- miR-135a acts as a tumor suppressor by targeting ASPH in endometrial cancer.International journal of clinical and experimental pathology · 2019Article
- Patient-Derived Xenograft Models for Endometrial Cancer Research.International journal of molecular sciences · 2018Review
- Fibroblast growth factor receptor 1 and 3 expression is associated with regulatory PI3K/AKT kinase activity, as well as invasion and prognosis, in human laryngeal cancer.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- miR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development.Journal of experimental & clinical cancer research : CR · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PI3K/AKT pathway plays an important role in the initiation and progression of cancer, and the drug development efforts targeting this pathway with therapeutic interventions have been advanced by academic and industrial groups. However, the clinical outcome is moderate. Combination of inhibition of PI3K/AKT and other targeted agents became a feasible approach. In this study we assessed the combined effect of ARQ 092, a pan-AKT inhibitor, and ARQ 087, a pan-FGFR inhibitor, in vitro and in vivo. In a panel of 45 cancer cell lines, on 24% (11 out of 45) the compounds showed synergistic effect, on 62% (28 out of 45) additive, and on 13% (6 out of 45) antagonistic. The highest percentage of synergism was found on endometrial and ovarian cancer cell lines. Mutational analysis revealed that PIK3CA/PIK3R1 mutations and aberrant activation of FGFR2 predicted synergism, whereas Ras mutations showed a reverse correlation. Pathway analysis revealed that a combination of ARQ 092 and ARQ 087 enhanced the inhibition of both the AKT and FGFR pathways in cell lines in which synergistic effects were found (AN3CA and IGROV-1). Cell cycle arrest and apoptotic response occurred only in AN3CA cell, and was not seen in IGROV-1 cells. Furthermore, enhanced antitumor activity was observed in mouse models with endometrial cancer cell line and patient-derived tumors when ARQ 092 and ARQ 087 were combined. These results from in-vitro and in-vivo studies provide a strong rationale in treating endometrial and other cancers with the activated PI3K/AKT and FGFR pathways.
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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.