ArticleOncotarget2016
OTX015 (MK-8628), a novel BET inhibitor, exhibits antitumor activity in non-small cell and small cell lung cancer models harboring different oncogenic mutations.
Article in Oncotarget, 2016. 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 30 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
30 citing papers in PubMed, 58 citations in OpenAlex.
- 3D chromatin architecture in cancer: mechanisms of dysregulation and emerging therapeutic strategies.Experimental & molecular medicine · 2026Review
- Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention.Stem cell reviews and reports · 2026Review
- Epigenetic Modulation of Immunity: Mechanisms, Implications, and Emerging Therapeutic Horizons; a Step Toward Epigenetics to Precision.Sub-cellular biochemistry · 2026Review
- Epigenomic Modulators and Thyroid Hormone Receptor β Agonists: A New Paradigm for Tumor Suppression in Thyroid Cancer.Endocrinology · 2025Review
- Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology.Genes & diseases · 2025Review
- Triple Combination of Entinostat, a Bromodomain Inhibitor, and Cisplatin Is a Promising Treatment Option for Bladder Cancer.Cancers · 2024Article
- Decoding the Epigenetics of Infertility: Mechanisms, Environmental Influences, and Therapeutic Strategies.Epigenomes · 2024Review
- Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer.Frontiers in pharmacology · 2024Review
- Role of c-Myc in lung cancer: Progress, challenges, and prospects.Chinese medical journal pulmonary and critical care medicine · 2023Article
- Streamlined DNA-encoded small molecule library screening and validation for the discovery of novel chemotypes targeting BET proteins.Molecular therapy. Nucleic acids · 2023Article
- Subtype classification based on t cell proliferation-related regulator genes and risk model for predicting outcomes of lung adenocarcinoma.Frontiers in immunology · 2023Article
- The synergistic anticancer effect of the bromodomain inhibitor OTX015 and histone deacetylase 6 inhibitor WT-161 in osteosarcoma.Cancer cell international · 2022Article
- Chemogenomics for drug discovery: clinical molecules from open access chemical probes.RSC chemical biology · 2021Review
- Targeting Epigenetics in Lung Cancer.Cold Spring Harbor perspectives in medicine · 2021Review
- The BET Inhibitor OTX015 Exhibits In Vitro and In Vivo Antitumor Activity in Pediatric Ependymoma Stem Cell Models.International journal of molecular sciences · 2021Article
- ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin-3 and NRXN3.Cancer communications (London, England) · 2020Article
- Oncogenic super-enhancer formation in tumorigenesis and its molecular mechanisms.Experimental & molecular medicine · 2020Review
- Small Molecules Targeting HATs, HDACs, and BRDs in Cancer Therapy.Frontiers in oncology · 2020Review
- Targeting transcription factors in cancer drug discovery.Exploration of targeted anti-tumor therapy · 2020Review
- Mission Possible: Advances in MYC Therapeutic Targeting in Cancer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitors targeting epigenetic control points of oncogenes offer a potential mean of blocking tumor progression in small cell and non-small cell lung carcinomas (SCLC, NSCLC). OTX015 (MK-8628) is a BET inhibitor selectively blocking BRD2/3/4. OTX015 was evaluated in a panel of NSCLC or SCLC models harboring different oncogenic mutations. Cell proliferation inhibition and cell cycle arrest were seen in sensitive NSCLC cells. MYC and MYCN were downregulated at both the mRNA and protein levels. In addition, OTX015-treatment significantly downregulated various stemness cell markers, including NANOG, Musashi-1, CD113 and EpCAM in H3122-tumors in vivo. Conversely, in SCLC models, weak antitumor activity was observed with OTX015, both in vitro and in vivo. No predictive biomarkers of OTX015 activity were identified in a large panel of candidate genes known to be affected by BET inhibition. In NSCLC models, OTX015 was equally active in both EML4-ALK positive and negative cell lines, whereas in SCLC models the presence of functional RB1 protein, which controls cell progression at G1, may be related to the final biological outcome of OTX015. Gene expression profiling in NSCLC and SCLC cell lines showed that OTX015 affects important genes and pathways with a very high overlapping between both sensitive and resistant cell lines. These data support the rationale for the OTX015 Phase Ib (NCT02259114) in solid tumors, where NSCLC patients with rearranged ALK gene or KRAS-positive mutations are currently being treated.
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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.