ArticleCancer letters2014
Loss-of-function RNAi screens in breast cancer cells identify AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 as sensitizing targets of rapamycin activity.
Article in Cancer letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 24 citations in OpenAlex.
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- Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells.Journal of cellular and molecular medicine · 2021Article
- Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer.Molecules (Basel, Switzerland) · 2021Review
- Influence of gene expression on survival of clear cell renal cell carcinoma.Cancer medicine · 2020Article
- The Identification of Key Gene Expression Signature and Biological Pathways in Metastatic Renal Cell Carcinoma.Journal of Cancer · 2020Article
- High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Co-targeting PLK1 and mTOR induces synergistic inhibitory effects against esophageal squamous cell carcinoma.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Bioinformatics analysis of gene expression profiles to identify causal genes in luminal B2 breast cancer.Oncology letters · 2017Article
- The Transcriptional Landscape of p53 Signalling Pathway.EBioMedicine · 2017Article
- Article
- Targeting therapeutic liabilities engendered by PIK3R1 mutations for cancer treatment.Pharmacogenomics · 2016Review
- PTK6 promotes hepatocellular carcinoma cell proliferation and invasion.American journal of translational research · 2016Article
- Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1.Cancers · 2015Review
- Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The use of molecularly targeted drugs as single agents has shown limited utility in many tumor types, largely due to the complex and redundant nature of oncogenic signaling networks. Targeting of the PI3K/AKT/mTOR pathway through inhibition of mTOR in combination with aromatase inhibitors has seen success in particular sub-types of breast cancer and there is a need to identify additional synergistic combinations to maximize the clinical potential of mTOR inhibitors. We have used loss-of-function RNAi screens of the mTOR inhibitor rapamycin to identify sensitizers of mTOR inhibition. RNAi screens conducted in combination with rapamycin in multiple breast cancer cell lines identified six genes, AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 that when silenced, each enhanced the sensitivity of multiple breast cancer lines to rapamycin. Using selective pharmacological agents we confirmed that inhibition of AURKB or PLK1 synergizes with rapamycin. Compound-associated gene expression data suggested histone deacetylation (HDAC) inhibition as a strategy for reducing the expression of several of the rapamycin-sensitizing genes, and we tested and validated this using the HDAC inhibitor entinostat in vitro and in vivo. Our findings indicate new approaches for enhancing the efficacy of rapamycin including the use of combining its application with HDAC inhibition.
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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.