ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
GSK690693 delays tumor onset and progression in genetically defined mouse models expressing activated Akt.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- lncRNA ENSRNOT00000087717 mediated differentiation of satellite glial cells derived from dorsal root ganglion via AKT1.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Roles of posttranslational modifications in lipid metabolism and cancer progression.Biomarker research · 2024Review
- Hyperglycemia-induced Sirt3 downregulation increases microglial aerobic glycolysis and inflammation in diabetic neuropathic pain pathogenesis.CNS neuroscience & therapeutics · 2024Article
- A targeted genetic modifier screen in Drosophila uncovers vulnerabilities in a genetically complex model of colon cancer.G3 (Bethesda, Md.) · 2023Article
- Dysregulated Smooth Muscle Cell BMPR2-ARRB2 Axis Causes Pulmonary Hypertension.Circulation research · 2023Article
- AKT inhibition sensitizes EVI1 expressing colon cancer cells to irinotecan therapy by regulating the Akt/mTOR axis.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagyFrontiers in pharmacology · 2022Article
- Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts.Scientific reports · 2021Article
- The biochemical and clinical implications of phosphatase and tensin homolog deleted on chromosome ten in different cancers.American journal of cancer research · 2021Review
- Polyphenolic Proanthocyanidin-B2 suppresses proliferation of liver cancer cells and hepatocellular carcinogenesis through directly binding and inhibiting AKT activity.Redox biology · 2020Article
- Article
- Article
- Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells.iScience · 2019Article
- DNA methylation in the central and efferent limbs of the chemoreflex requires carotid body neural activity.The Journal of physiology · 2018Article
- Expanding primary cells from mucoepidermoid and other salivary gland neoplasms for genetic and chemosensitivity testing.Disease models & mechanisms · 2018Article
- AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma.The American journal of pathology · 2017Article
- Integrin β3/Akt signaling contributes to platelet-induced hemangioendothelioma growth.Scientific reports · 2017Article
- The homeoprotein Dlx5 drives murine T-cell lymphomagenesis by directly transactivating Notch and upregulating Akt signaling.Oncotarget · 2017Article
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
purposeAkt plays a central role in regulating tumor cell survival and cell cycle progression and is regarded as a promising therapeutic target. We used genetically defined mouse models that develop spontaneous tumors exhibiting activated Akt to determine if Akt inhibition by GSK690693 is effective in the treatment of cancer. The broad long-term objective of this project was to use preclinical cancer models with precisely defined genetic lesions to elucidate the efficacy of targeting Akt with GSK690693. EXPERIMENTAL
designWe tested the in vivo effects of GSK690693 in Lck-MyrAkt2 transgenic mice that develop lymphomas, heterozygous Pten(+/-) knockout mice that exhibit endometrial tumors, and TgMISIIR-TAg-DR26 mice that develop ovarian carcinomas, all of which exhibit hyperactivation of Akt. In addition to standard disease onset and histology, tumors arising in treated animals were examined by immunohistochemistry to verify downregulated Akt signaling relative to placebo-treated mice. When possible, drug response was evaluated in tumor cell cultures by standard proliferation and apoptosis assays and by immunoblotting with various phosphospecific antibodies.
resultsGSK690693 exhibited efficacy irrespective of the mechanism of Akt activation involved. Interestingly, GSK690693 was most effective in delaying tumor progression in Lck-MyrAkt2 mice expressing a membrane-bound, constitutively active form of Akt. Both tumors and primary cell cultures displayed downregulation of the Akt pathway, increased apoptosis, and primarily decreased cell proliferation.
conclusionThese results suggest that GSK690693 or other Akt inhibitors might have therapeutic efficacy in human cancers with hyperactivated Akt and/or a dependence on Akt signaling for tumor progression.
Indexed as
Identifiers
What OpenQuestion holds
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.