ArticleCancer research2014
Combined SFK/mTOR inhibition prevents rapamycin-induced feedback activation of AKT and elicits efficient tumor regression.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy.Cancers · 2022Article
- Experimental and computational assessment of the synergistic pharmacodynamic drug-drug interactions of a triple combination therapy in refractory HER2-positive breast cancer cells.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations.American journal of cancer research · 2022Article
- Kahweol Induces Apoptosis in Hepatocellular Carcinoma Cells by Inhibiting the Src/mTOR/STAT3 Signaling Pathway.International journal of molecular sciences · 2021Article
- Advances in Understanding of the Copper Homeostasis inInternational journal of molecular sciences · 2021Review
- Targeting LRIG2 overcomes resistance to EGFR inhibitor in glioblastoma by modulating GAS6/AXL/SRC signaling.Cancer gene therapy · 2020Article
- RICTOR/mTORC2 affects tumorigenesis and therapeutic efficacy of mTOR inhibitors in esophageal squamous cell carcinoma.Acta pharmaceutica Sinica. B · 2020Article
- Review
- Combination therapy with mTOR kinase inhibitor and dasatinib as a novel therapeutic strategy for vestibular schwannoma.Scientific reports · 2020Article
- Src Family Kinase Inhibitors Block Translation of Alphavirus Subgenomic mRNAs.Antimicrobial agents and chemotherapy · 2019Article
- Targeting mTOR and Src restricts hepatocellular carcinoma growth in a novel murine liver cancer model.PloS one · 2019Article
- ETV7 is an essential component of a rapamycin-insensitive mTOR complex in cancer.Science advances · 2018Article
- Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer.Oncogenesis · 2018Article
- Utility of a Novel Three-Dimensional and Dynamic (3DD) Cell Culture System for PK/PD Studies: Evaluation of a Triple Combination Therapy at Overcoming Anti-HER2 Treatment Resistance in Breast Cancer.Frontiers in pharmacology · 2018Article
- Qianlie Xiaozheng Decoction Induces Autophagy in Human Prostate Cancer Cells via Inhibition of the Akt/mTOR Pathway.Frontiers in pharmacology · 2018Article
- GAS6-expressing and self-sustaining cancer cells in 3D spheroids activate the PDK-RSK-mTOR pathway for survival and drug resistance.Molecular oncology · 2017Article
- Adaptive metabolic rewiring to chronic SFK inhibition.Oncotarget · 2017Article
- Inhibition of p70S6K does not mimic the enhancement of Akt phosphorylation by rapamycin.Heliyon · 2017Article
- Dasatinib modulates sensitivity to pemetrexed in malignant pleural mesothelioma cell lines.Oncotarget · 2016Article
- Inhibition of epithelial-mesenchymal transition in bladder cancer cells via modulation of mTOR signalling.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Resistance to receptor tyrosine kinase (RTK) blockade in breast cancer is often mediated by activation of bypass pathways that sustain growth. Src and mammalian target of rapamycin (mTOR) are two intrinsic targets that are downstream of most RTKs. To date, limited clinical efficacy has been observed with either Src or mTOR inhibitors when used as single agents. Resistance to mTOR inhibitors is associated with loss of negative feedback regulation, resulting in phosphorylation and activation of AKT. Herein, we describe a novel role for Src in contributing to rapalog-induced AKT activation. We found that dual activation of Src and the mTOR pathway occurs in nearly half of all breast cancers, suggesting potential cross-talk. As expected, rapamycin inhibition of mTOR results in feedback activation of AKT in breast cancer cell lines. Addition of the Src/c-Abl inhibitor, dasatinib, completely blocks this feedback activation, confirming convergence between Src and the mTOR pathway. Analysis in vivo revealed that dual Src and mTOR inhibition is highly effective in two mouse models of breast cancer. In a luminal disease model, combined dasatinib and rapamycin is more effective at inducing regression than either single agent. Furthermore, the combination of dasatinib and rapamycin delays tumor recurrence following the cessation of treatment. In a model of human EGFR-2-positive (HER2(+)) disease, dasatinib alone is ineffective, but potentiates the efficacy of rapamycin. These data suggest that combining mTOR and Src inhibitors may provide a new approach for treating multiple breast cancer subtypes that may circumvent resistance to targeted RTK therapies.
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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.