ArticleOncotarget2015
Activation of PI3K/Akt/mTOR signaling in the tumor stroma drives endocrine therapy-dependent breast tumor regression.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 2 of them syntheses that pooled it.
What it found
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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
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- MARCKS contributes to stromal cancer-associated fibroblast activation and facilitates ovarian cancer metastasis.Oncotarget · 2016Pooled it
- mTOR inhibitors, a new era for metastatic luminal HER2-negative breast cancer? A systematic review and a meta-analysis of randomized trials.Oncotarget · 2016Pooled it
- Cerebral Cavernous Malformation: From Genetics to Pharmacotherapy.Brain and behavior · 2025Review
- Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.Journal of translational medicine · 2024Review
- Microarray-based Detection of Critical Overexpressed Genes in the Progression of Hepatic Fibrosis in Non-alcoholic Fatty Liver Disease: A Protein-protein Interaction Network Analysis.Current medicinal chemistry · 2024Article
- Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations.Journal of personalized medicine · 2023Review
- Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models.Scientific reports · 2023Article
- Inhibiting PI3K-AKT-mTOR Signaling in Multiple Myeloma-Associated Mesenchymal Stem Cells Impedes the Proliferation of Multiple Myeloma Cells.Frontiers in oncology · 2022Article
- Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway.Scientific reports · 2021Article
- AKT isoforms have discrete expression in triple negative breast cancers and roles in cisplatin sensitivity.Oncotarget · 2020Article
- Targeted next generation sequencing identifies somatic mutations in a cohort of Egyptian breast cancer patients.Journal of advanced research · 2020Article
- Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals.Breast cancer research and treatment · 2019Review
- PI3K/Akt/mTOR signalling pathway activation in patients with ER-positive, metachronous, contralateral breast cancer treated with hormone therapy.Oncology letters · 2019Article
- Salvianolic acid A attenuates CClDrug design, development and therapy · 2019Article
- Phosphoinositide 3-Kinase Signaling Pathway in Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, and Therapeutics.Frontiers in physiology · 2018Review
- Downregulation of BZW2 inhibits osteosarcoma cell growth by inactivating the Akt/mTOR signaling pathway.Oncology reports · 2017Article
- AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins.Scientific reports · 2017Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Improved efficacy of neoadjuvant endocrine-targeting therapies in luminal breast carcinomas could be achieved with optimal use of pathway targeting agents. In a mouse model of ductal breast carcinoma we identify a tumor regressive stromal reaction that is induced by neoadjuvant endocrine therapy. This reparative reaction is characterized by tumor neovascularization accompanied by infiltration of immune cells and carcinoma-associated fibroblasts that stain for phosphorylated ribosomal protein S6 (pS6), downstream the PI3K/Akt/mTOR pathway. While tumor variants with higher PI3K/Akt/mTOR activity respond well to a combination of endocrine and PI3K/Akt/mTOR inhibitors, tumor variants with lower PI3K/Akt/mTOR activity respond more poorly to the combination therapy than to the endocrine therapy alone, associated with inhibition of stromal pS6 and the reparative reaction. In human breast cancer xenografts we confirm that such differential sensitivity to therapy is primarily determined by the level of PI3K/Akt/mTOR in tumor cells. We further show that the clinical response of breast cancer patients undergoing neoadjuvant endocrine therapy is associated with the reparative stromal reaction. We conclude that tumor level and localization of pS6 are associated with therapeutic response in breast cancer and represent biomarkers to distinguish which tumors will benefit from the incorporation of PI3K/Akt/mTOR inhibitors with neoadjuvant endocrine therapy.
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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.