ArticleScientific reports2017
PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
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- Chemical composition of essential and fixed oils of Tagetes erecta fruits (Iran) and their implications in inhibition of cancer signaling.Scientific reports · 2024Article
- STING activation increases the efficiency of temozolomide in PTEN harbouring glioblastoma cells.Turkish journal of medical sciences · 2024Article
- Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance.International journal of molecular sciences · 2023Review
- BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.Frontiers in oncology · 2023Review
- PDGF, NGF, and EGF as main contributors to tumorigenesis in high-risk retinoblastoma.Frontiers in oncology · 2023Article
- Fibroblast-Induced Paradoxical PI3K Pathway Activation in PTEN-Competent Colorectal Cancer: Implications for Therapeutic PI3K/mTOR Inhibition.Frontiers in oncology · 2022Article
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- Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus.Antioxidants (Basel, Switzerland) · 2020Article
- MEK is a promising target in the basal subtype of bladder cancer.Oncotarget · 2020Article
- KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities.Journal of experimental & clinical cancer research : CR · 2020Review
- Identification of a Triple Drug Combination That Is Synergistically Cytotoxic for Triple-Negative Breast Cancer Cells Using a Novel Combination Discovery Approach.SLAS discovery : advancing life sciences R & D · 2020Article
- PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy.International journal of molecular sciences · 2020Review
- Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains.Cancers · 2020Article
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- Patient-specific logic models of signaling pathways from screenings on cancer biopsies to prioritize personalized combination therapies.Molecular systems biology · 2020Article
- From Genetic Alterations to Tumor Microenvironment: The Ariadne's String in Pancreatic Cancer.Cells · 2020Review
Corrections and comments
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Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoproteomic profile modification(s) in response to combined MEK/mTOR inhibition in PTEN-loss contexts and identified JAK1/STAT3 activation as a potential mediator of synergistic interactions. Overall, our results show that PTEN-loss is a crucial determinant of synergistic interactions between MAPK and PI3K pathway inhibitors, potentially exploitable for the selection of cancer patients at the highest chance of benefit from combined therapeutic strategies.
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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.