ArticleOncotarget2017
The bromodomain inhibitor OTX015 (MK-8628) exerts anti-tumor activity in triple-negative breast cancer models as single agent and in combination with everolimus.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02259114 (A Phase IB Trial With OTX015/MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal), which is not on this map. Cited by 52 papers.
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.
A Phase IB Trial With OTX015/MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Patients With Selected Advanced Solid Tumors
Who cites it
52 citing papers in PubMed, 92 citations in OpenAlex.
- Combinational BET and mTOR inhibition unveils EGR1 as acute myeloid leukemia prognostic biomarker.Scientific reports · 2025Article
- Tailored therapies for triple-negative breast cancer: current landscape and future perceptions.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting Triple-Negative Breast Cancer: Resistance Mechanisms and Therapeutic Advancements.Cancer medicine · 2025Review
- The role of the mTOR pathway in breast cancer stem cells (BCSCs): mechanisms and therapeutic potentials.Stem cell research & therapy · 2025Review
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- Targeting the Molecules in EMT: A Potential Therapeutic Opportunity in Breast Cancer.Current molecular medicine · 2025Review
- Beyond the Usual Suspects: Examining the Role of Understudied Histone Variants in Breast Cancer.International journal of molecular sciences · 2024Review
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- Regulation of Cell Plasticity by Bromodomain and Extraterminal Domain (BET) Proteins: A New Perspective in Glioblastoma Therapy.International journal of molecular sciences · 2023Review
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- Review
- Advancements in the Treatment of Triple-Negative Breast Cancer: A Narrative Review of the Literature.Cureus · 2022Review
- Epigenetic Therapies and Biomarkers in Breast Cancer.Cancers · 2022Review
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
- Article
- Review
- Functional Roles of Bromodomain Proteins in Cancer.Cancers · 2021Review
- Chemogenomics for drug discovery: clinical molecules from open access chemical probes.RSC chemical biology · 2021Review
- Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models. The aim of this study was to evaluate the anti-tumor activity of OTX015 as single agent and in combination with everolimus in TNBC models. OTX015 was assayed in three human TNBC-derived cell lines, HCC1937, MDA-MB-231 and MDA-MB-468, all showing antiproliferative activity after 72 h (GI50 = 75-650 nM). This was accompanied by cell cycle arrest and decreased expression of cancer stem cells markers. However, c-MYC protein and mRNA levels were only down-regulated in MDA-MB-468 cells. Gene set enrichment analysis showed up-regulation of genes involved in epigenetic control of transcription, chromatin and the cell cycle, and down-regulation of stemness-related genes. In vitro, combination with everolimus was additive in HCC1937 and MDA-MB-231 cells, but antagonistic in MDA-MB-468 cells. In MDA-MB-231 murine xenografts, tumor mass was significantly (p < 0.05) reduced by OTX015 with respect to vehicle-treated animals (best T/C = 40.7%). Although everolimus alone was not active, the combination was more effective than OTX015 alone (best T/C = 20.7%). This work supports current clinical trials with OTX015 in TNBC (NCT02259114).
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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.