ArticleMolecular oncology2014
TORC1 and class I HDAC inhibitors synergize to suppress mature B cell neoplasms.
Article in Molecular oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Targeted intervention of tumor microenvironment with HDAC inhibitors and their combination therapy strategies.European journal of medical research · 2025Review
- The mTOR Signaling Pathway and mTOR Inhibitors in Cancer: Next-generation Inhibitors and Approaches.Current molecular medicine · 2024Review
- Drug combinations identified by high-throughput screening promote cell cycle transition and upregulate Smad pathways in myeloma.Cancer letters · 2023Article
- Structural Optimization and Anticancer Activity of Polo-like Kinase 1 (Plk1) Polo-Box Domain (PBD) Inhibitors and Their Prodrugs.ACS pharmacology & translational science · 2023Article
- Identification of solamargine as a cisplatin sensitizer through phenotypical screening in cisplatin-resistant NSCLC organoids.Frontiers in pharmacology · 2022Article
- Article
- Hypomorphic mTOR Downregulates CDK6 and Delays Thymic Pre-T LBL Tumorigenesis.Molecular cancer therapeutics · 2020Article
- Mouse tumor susceptibility genes identify drug combinations for multiple myeloma.Journal of cancer metastasis and treatment · 2020Article
- Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt lymphoma.Scientific reports · 2018Article
- Review
- Cladribine in combination with entinostat synergistically elicits anti-proliferative/anti-survival effects on multiple myeloma cells.Cell cycle (Georgetown, Tex.) · 2018Article
- Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation.Molecular cancer therapeutics · 2017Article
- Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents.Oncotarget · 2016Review
- Small Molecule Microarrays Enable the Identification of a Selective, Quadruplex-Binding Inhibitor of MYC Expression.ACS chemical biology · 2016Article
- Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment.Oncotarget · 2015Article
- Histone acetyltransferases and histone deacetylases in B- and T-cell development, physiology and malignancy.Genes & cancer · 2015Review
- Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study.Haematologica · 2015Article
- mTOR kinase inhibitors synergize with histone deacetylase inhibitors to kill B-cell acute lymphoblastic leukemia cells.Oncotarget · 2015Article
- Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer.Molecular oncology · 2014Article
- Loss-of-function RNAi screens in breast cancer cells identify AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 as sensitizing targets of rapamycin activity.Cancer letters · 2014Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Enhanced proliferative signaling and loss of cell cycle regulation are essential for cancer progression. Increased mitogenic signaling through activation of the mTOR pathway, coupled with deregulation of the Cyclin D/retinoblastoma (Rb) pathway is a common feature of lymphoid malignancies, including plasmacytoma (PCT), multiple myeloma (MM), Burkitt's lymphoma (BL), and mantle cell lymphoma (MCL). Here we evaluate the synergy of pharmacologically affecting both of these critical pathways using the mTOR inhibitor sirolimus and the histone deacetylase inhibitor entinostat. A dose-matrix screening approach found this combination to be highly active and synergistic in a panel of genetically diverse human MM cell lines. Synergy and activity was observed in mouse PCT and human BL and MCL cell lines tested in vitro, as well as in freshly isolated primary MM patient samples tested ex vivo. This combination had minimal effects on healthy donor cells and retained activity when tested in a co-culture system simulating the protective interaction of cancer cells with the tumor microenvironment. Combining sirolimus with entinostat enhanced cell cycle arrest and apoptosis. At the molecular level, entinostat increased the expression of cell cycle negative regulators including CDKN1A (p21) and CDKN2A (p16), while the combination decreased critical growth and survival effectors including Cyclin D, BCL-XL, BIRC5, and activated MAPK.
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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.