ArticleMolecular cancer therapeutics2011
Compensatory pathways induced by MEK inhibition are effective drug targets for combination therapy against castration-resistant prostate cancer.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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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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
33 citing papers in PubMed, 65 citations in OpenAlex.
- MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors.The Journal of clinical investigation · 2013Trial
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- Molecular Targeted Therapies in Metastatic Prostate Cancer: Recent Advances and Future Challenges.Cancers · 2023Review
- From Therapy Resistance to Targeted Therapies in Prostate Cancer.Frontiers in oncology · 2022Review
- Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response.Scientific reports · 2021Article
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- TPL2 enforces RAS-induced inflammatory signaling and is activated by point mutations.The Journal of clinical investigation · 2020Article
- CUDC-907, a novel dual PI3K and HDAC inhibitor, in prostate cancer: Antitumour activity and molecular mechanism of action.Journal of cellular and molecular medicine · 2020Article
- The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling.International journal of molecular sciences · 2020Review
- Predicting effective drug combinations using gradient tree boosting based on features extracted from drug-protein heterogeneous network.BMC bioinformatics · 2019Article
- Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2.Frontiers in endocrinology · 2019Article
- Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened.Frontiers in genetics · 2019Review
- Krukovine Suppresses KRAS-Mutated Lung Cancer Cell Growth and Proliferation by Inhibiting the RAF-ERK Pathway and Inactivating AKT Pathway.Frontiers in pharmacology · 2018Article
- Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate cancer.Oncotarget · 2017Article
- Microenvironmental agonists generateBlood advances · 2017Article
- Quantitative Proteomics Reveals Fundamental Regulatory Differences in Oncogenic HRAS and Isocitrate Dehydrogenase (IDH1) Driven Astrocytoma.Molecular & cellular proteomics : MCP · 2017Article
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- miR-155 Controls Lymphoproliferation in LAT Mutant Mice by Restraining T-Cell Apoptosis via SHIP-1/mTOR and PAK1/FOXO3/BIM Pathways.PloS one · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Targeted therapies have often given disappointing results when used as single agents in solid tumors, suggesting the importance of devising rational combinations of targeted drugs. We hypothesized that construction of such combinations could be guided by identification of growth and survival pathways whose activity or expression become upregulated in response to single-agent drug treatment. We mapped alterations in signaling pathways assessed by gene array and protein phosphorylation to identify compensatory signal transduction pathways in prostate cancer xenografts treated with a MAP/ERK kinase (MEK) inhibitor PD325901. In addition to numerous components of the extracellular signal-regulated kinase (ERK) signaling pathway, components of the IKK, hedgehog, and phosphoinositide 3-kinase/Akt/mTOR pathways were upregulated following treatment with PD325901. Combinations of PD325901 with inhibitors of any one of these upregulated pathways provided synergistically greater growth inhibition of in vitro cell growth and survival than the individual drugs alone. Thus, the identification of compensatory signal transduction pathways paves the way for rational combinatorial therapies for the effective treatment of prostate cancer.
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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.