ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Preclinical testing of PI3K/AKT/mTOR signaling inhibitors in a mouse model of ovarian endometrioid adenocarcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
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- Cancer metastases: Tailoring the targets.Heliyon · 2024Review
- Photobiomodulation therapy moderates cancer cachexia-associated muscle wasting through activating PI3K/AKT/FoxO3a pathway.Apoptosis : an international journal on programmed cell death · 2024Article
- The multifaced role and therapeutic regulation of autophagy in ovarian cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-International journal of nanomedicine · 2023Article
- Targeted Sequencing of Plasma-Derived vs. Urinary cfDNA from Patients with Triple-Negative Breast Cancer.Cancers · 2022Article
- The role of PI3'-lipid signalling in melanoma initiation, progression and maintenance.Experimental dermatology · 2022Review
- Comprehending the Proteomic Landscape of Ovarian Cancer: A Road to the Discovery of Disease Biomarkers.Proteomes · 2021Review
- Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma.Open life sciences · 2021Article
- CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary.Cancers · 2019Article
- Activation of p70S6 Kinase-1 in Mesenchymal Stem Cells Is Essential to Lung Tissue Repair.Stem cells translational medicine · 2018Article
- Clinical sequencing using a next-generation sequencing-based multiplex gene assay in patients with advanced solid tumors.Cancer science · 2017Article
- Alendronate-anchored PEGylation of ceria nanoparticles promotes human hepatoma cell proliferation via AKT/ERK signaling pathways.Cancer medicine · 2017Article
- Recent Advances in Understanding, Diagnosing, and Treating Ovarian Cancer.F1000Research · 2017Review
- The rise of genomic profiling in ovarian cancer.Expert review of molecular diagnostics · 2016Review
- Impact of oviductal versus ovarian epithelial cell of origin on ovarian endometrioid carcinoma phenotype in the mouse.The Journal of pathology · 2016Article
- New models of hematogenous ovarian cancer metastasis demonstrate preferential spread to the ovary and a requirement for the ovary for abdominal dissemination.Translational research : the journal of laboratory and clinical medicine · 2016Article
- The anti-ovarian cancer activity by WYE-132, a mTORC1/2 dual inhibitor.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Novel reversible selective inhibitor of CRM1 for targeted therapy in ovarian cancer.Journal of ovarian research · 2015Article
- Unremitting cell proliferation in the secretory phase of eutopic endometriosis: involvement of pAkt and pGSK3β.Reproductive sciences (Thousand Oaks, Calif.) · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeGenetically engineered mouse (GEM) models of ovarian cancer that closely recapitulate their human tumor counterparts may be invaluable tools for preclinical testing of novel therapeutics. We studied murine ovarian endometrioid adenocarcinomas (OEA) arising from conditional dysregulation of canonical WNT and PI3K/AKT/mTOR pathway signaling to investigate their response to conventional chemotherapeutic drugs and mTOR or AKT inhibitors. EXPERIMENTAL
designOEAs were induced by injection of adenovirus expressing Cre recombinase (AdCre) into the ovarian bursae of Apc(flox/flox); Pten(flox/flox) mice. Tumor-bearing mice or murine OEA-derived cell lines were treated with cisplatin and paclitaxel, mTOR inhibitor rapamycin, or AKT inhibitors API-2 or perifosine. Treatment effects were monitored in vivo by tumor volume and bioluminescence imaging, in vitro by WST-1 proliferation assays, and in OEA tissues and cells by immunoblotting and immunostaining for levels and phosphorylation status of PI3K/AKT/mTOR signaling pathway components.
resultsMurine OEAs developed within 3 weeks of AdCre injection and were not preceded by endometriosis. OEAs responded to cisplatin + paclitaxel, rapamycin, and AKT inhibitors in vivo. In vitro studies showed that response to mTOR and AKT inhibitors, but not conventional cytotoxic drugs, was dependent on the status of PI3K/AKT/mTOR signaling. AKT inhibition in APC(-)/Pten(-) tumor cells resulted in compensatory upregulation of ERK signaling.
conclusionsThe studies show the utility of this GEM model of ovarian cancer for preclinical testing of novel PI3K/AKT/mTOR signaling inhibitors and provide evidence for compensatory signaling, suggesting that multiple rather than single agent targeted therapy will be more efficacious for treating ovarian cancers with activated PI3K/AKT/mTOR signaling.
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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.