ArticleOncotarget2015
Epithelial to mesenchymal transition is associated with rapamycin resistance.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- ONC201/TIC10 enhances durability of mTOR inhibitor everolimus in metastatic ER+ breast cancer.eLife · 2023Article
- Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy.Cancers · 2022Article
- CTCF Expression and Dynamic Motif Accessibility Modulates Epithelial-Mesenchymal Gene Expression.Cancers · 2022Article
- mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?Frontiers of medicine · 2021Review
- Article
- Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities.Nature reviews. Urology · 2019Review
- Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models.Scientific reports · 2019Article
- Rapalog resistance is associated with mesenchymal-type changes in Tsc2-null cells.Scientific reports · 2019Article
- A Population of Heterogeneous Breast Cancer Patient-Derived Xenografts Demonstrate Broad Activity of PARP Inhibitor in BRCA1/2 Wild-Type Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells.Oncotarget · 2017Article
- Article
- Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.Oncogene · 2017Article
- mTOR function and therapeutic targeting in breast cancer.American journal of cancer research · 2017Review
- The therapeutic potential of mTOR inhibitors in breast cancer.British journal of clinical pharmacology · 2016Review
- miR-206 regulates cisplatin resistance and EMT in human lung adenocarcinoma cells partly by targeting MET.Oncotarget · 2016Article
- Simultaneous Targeting of Bladder Tumor Growth, Survival, and Epithelial-to-Mesenchymal Transition with a Novel Therapeutic Combination of Acetazolamide (AZ) and Sulforaphane (SFN).Targeted oncology · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Rapamycin analogues have antitumor efficacy in several tumor types, however few patients demonstrate tumor regression. Thus, there is a pressing need for markers of intrinsic response/resistance and rational combination therapies. We hypothesized that epithelial-to-mesenchymal transition (EMT) confers rapamycin resistance. We found that the epithelial marker E-cadherin protein is higher in rapamycin sensitive (RS) cells and mesenchymal breast cancer cell lines selected by transcriptional EMT signatures are less sensitive to rapamycin. MCF7 cells, transfected with constitutively active mutant Snail, had increased rapamycin resistance (RR) compared to cells transfected with wild-type Snail. Conversely, we transfected two RR mesenchymal cell lines-ACHN and MDA-MB-231-with miR-200b/c or ZEB1 siRNA to promote mesenchymal-to-epithelial transition. This induced E-cadherin expression in both cell lines, and ACHN demonstrated a significant increase in RS. Treatment of ACHN and MDA-MB-231 with trametinib modulated EMT in ACHN cells in vitro. Treatment of MDA-MB-231 and ACHN xenografts with trametinib in combination with rapamycin resulted in significant growth inhibition in both but without an apparent effect on EMT. Future studies are needed to determine whether EMT status is predictive of sensitivity to rapalogs and to determine whether combination therapy with EMT modulating agents can enhance antitumor effects of PI3K/mTOR inhibitors.
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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.