ArticleMolecular cancer therapeutics2017
Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation.
Article in Molecular cancer therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Entinostat plus Pembrolizumab in Patients with Metastatic NSCLC Previously Treated with Anti-PD-(L)1 Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Large-scale human myeloma cell line small molecule compound screen dataset.Scientific data · 2025Article
- The dual HDAC/PI3K inhibitor CUDC-907 inhibits the growth and proliferation of MYC-driven Group 3 medulloblastoma.Cell death discovery · 2025Article
- A structure-based designed small molecule depletes hRpn13Nature communications · 2024Article
- Article
- Research Progress on Pyroptosis in Hematological Malignancies.Current treatment options in oncology · 2023Review
- Drug combinations identified by high-throughput screening promote cell cycle transition and upregulate Smad pathways in myeloma.Cancer letters · 2023Article
- Exploring the mTOR Signalling Pathway and Its Inhibitory Scope in Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention.Drug discovery today · 2022Review
- Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours.Nature communications · 2021Article
- Therapeutic Potential of CUDC-907 (Fimepinostat) for Hepatocarcinoma Treatment Revealed by Tumor Spheroids-Based Drug Screening.Frontiers in pharmacology · 2021Article
- MYC inhibitors in multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Article
- Hypomorphic mTOR Downregulates CDK6 and Delays Thymic Pre-T LBL Tumorigenesis.Molecular cancer therapeutics · 2020Article
- Chronic Sulforaphane Administration Inhibits Resistance to the mTOR-Inhibitor Everolimus in Bladder Cancer Cells.International journal of molecular sciences · 2020Article
- Curcumin-A Viable Agent for Better Bladder Cancer Treatment.International journal of molecular sciences · 2020Review
- Mouse tumor susceptibility genes identify drug combinations for multiple myeloma.Journal of cancer metastasis and treatment · 2020Article
- Review
- Low levels of pyruvate induced by a positive feedback loop protects cholangiocarcinoma cells from apoptosis.Cell communication and signaling : CCS · 2019Article
- Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.Cancers · 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
20 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared with single agents. In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared with single agents. Mice bearing plasma cell tumors lived an average of 70 days longer on combination treatment compared with single agents. A set of 37 genes cooperatively affected (34 downregulated; 3 upregulated) by the combination responded pharmacodynamically in human myeloma cell lines, xenografts, and a P493 model, and were both enriched in tumors, and correlated with prognostic markers in myeloma patient datasets. Genes downregulated by the combination were overexpressed in several untreated cancers (breast, lung, colon, sarcoma, head and neck, myeloma) compared with normal tissues. The MYC/E2F axis, identified by upstream regulator analyses and validated by immunoblots, was significantly inhibited by the drug combination in several myeloma cell lines. Furthermore, 88% of the 34 genes downregulated have MYC-binding sites in their promoters, and the drug combination cooperatively reduced MYC half-life by 55% and increased degradation. Cells with MYC mutations were refractory to the combination. Thus, integrative approaches to understand drug synergy identified a clinically actionable strategy to inhibit MYC/E2F activity and tumor cell growth
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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.