ArticleFrontiers in oncology2017
Efficacy and Molecular Mechanisms of Differentiated Response to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Models of p53-Mutated Triple-Negative Breast Cancer.
Article in Frontiers in oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis 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.
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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Pooled it
- A phase II clinical trial of the Aurora and angiogenic kinase inhibitor ENMD-2076 for previously treated, advanced, or metastatic triple-negative breast cancer.Breast cancer research : BCR · 2018Trial
- Article
- Targeting Senescence as a Therapeutic Opportunity for Triple-Negative Breast Cancer.Molecular cancer therapeutics · 2023Review
- ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer.BMC cancer · 2022Article
- Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies.Journal of hematology & oncology · 2022Review
- Oxethazaine inhibits esophageal squamous cell carcinoma proliferation and metastasis by targeting aurora kinase A.Cell death & disease · 2022Article
- Current methods in translational cancer research.Cancer metastasis reviews · 2021Review
- Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy.Molecular cancer · 2021Review
- Preclinical and Dose-Finding Phase I Trial Results of Combined Treatment with a TORC1/2 Inhibitor (TAK-228) and Aurora A Kinase Inhibitor (Alisertib) in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Article
- Wee1 Inhibition Enhances the Anti-Tumor Effects of Capecitabine in Preclinical Models of Triple-Negative Breast Cancer.Cancers · 2020Article
- Article
- First-in-Class Phosphorylated-p68 Inhibitor RX-5902 Inhibits β-Catenin Signaling and Demonstrates Antitumor Activity in Triple-Negative Breast Cancer.Molecular cancer therapeutics · 2019Article
- Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple-negative breast cancer.Journal of cellular and molecular medicine · 2019Article
- Aurora-A/ERK1/2/mTOR axis promotes tumor progression in triple-negative breast cancer and dual-targeting Aurora-A/mTOR shows synthetic lethality.Cell death & disease · 2019Article
- Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells.Oncology research · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTriple-negative breast cancer (TNBC) is a subtype associated with poor prognosis and for which there are limited therapeutic options. The purpose of this study was to evaluate the efficacy of ENMD-2076 in p53-mutated TNBC patient-derived xenograft (PDX) models and describe patterns of terminal cell fate in models demonstrating sensitivity, intrinsic resistance, and acquired resistance to ENMD-2076. EXPERIMENTAL
designp53-mutated, TNBC PDX models were treated with ENMD-2076 and evaluated for mechanisms of sensitivity or resistance to treatment. Correlative tissue testing was performed on tumor tissue to assess for markers of proliferation, apoptosis, senescence, and pathways of resistance after treatment and at the time of acquired resistance.
resultsSensitivity to ENMD-2076 200 mg/kg daily was associated with induction of apoptosis while models exhibiting intrinsic or acquired resistance to treatment presented with a senescent phenotype. Response to ENMD-2076 was accompanied by an increase in p53 and p73 levels, even within the background of mutant p53. Treatment with ENMD-2076 resulted in a decrease in pAurA and an increase in pHH3. We observed a TNBC subtype switch from the luminal androgen receptor to the basal-like subtype at acquired resistance.
conclusionENMD-2076 has antitumor activity in preclinical models of p53-mutated TNBC. Increased levels of p53 and p73 correlated with sensitivity whereas senescence was associated with resistance to ENMD-2076. The novel finding of a TNBC subtype switch at time of acquired resistance may provide mechanistic insights into the biologic effects of selective pressure of anticancer treatments on TNBC. ENMD-2076 is currently being evaluated in a Phase 2 clinical trial in patients with metastatic, previously treated TNBC where these biologic correlates can be further explored.
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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.