ReviewISRN oncology2013
Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins.
Review in ISRN oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- IκBα kinase inhibitor BAY 11-7082 promotes anti-tumor effect in RAS-driven cancers.Journal of translational medicine · 2024Article
- PHLDA1 promotes glioblastoma cell growth via sustaining the activation state of Ras.Cellular and molecular life sciences : CMLS · 2022Article
- Mechanism of activation and the rewired network: New drug design concepts.Medicinal research reviews · 2022Review
- Inhibition of Nonfunctional Ras.Cell chemical biology · 2021Review
- Sprouty4 negatively regulates ERK/MAPK signaling and the transition from in situ to invasive breast ductal carcinoma.PloS one · 2021Article
- Targeting the Small GTPase Superfamily through Their Regulatory Proteins.Angewandte Chemie (International ed. in English) · 2020Review
- Fitness of unregulated human Ras mutants modeled by implementing computational mutagenesis and machine learning techniques.Heliyon · 2019Article
- Breaking the Fourth Wall: Modulating Quaternary Associations for Protein Regulation and Drug Discovery.Chembiochem : a European journal of chemical biology · 2019Review
- Ras and Rap1: A tale of two GTPases.Seminars in cancer biology · 2019Review
- Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening.Experimental neurology · 2018Article
- Phosphorylation of the C-Raf N Region Promotes Raf Dimerization.Molecular and cellular biology · 2017Article
- How to Target Activated Ras Proteins: Direct Inhibition vs. Induced Mislocalization.Mini reviews in medicinal chemistry · 2016Review
- Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis.Nature communications · 2015Article
- MicroRNA-Based Therapeutic Strategies for Targeting Mutant and Wild Type RAS in Cancer.Drug development research · 2015Review
- KRAS and HRAS mutations confer resistance to MET targeting in preclinical models of MET-expressing tumor cells.Molecular oncology · 2015Article
- MicroRNA 17-92 cluster mediates ETS1 and ETS2-dependent RAS-oncogenic transformation.PloS one · 2014Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The ability to selectively and directly target activated Ras would provide immense utility for treatment of the numerous cancers that are driven by oncogenic Ras mutations. Patients with disorders driven by overactivated wild-type Ras proteins, such as type 1 neurofibromatosis, might also benefit from progress made in that context. Activated Ras is an extremely challenging direct drug target due to the inherent difficulties in disrupting the protein:protein interactions that underlie its activation and function. Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials. Likely reasons for this disappointing outcome include the significant and underappreciated differences in the isoforms of Ras. It is still plausible that inhibition of farnesyl transferase will prove effective for disease that is driven by activated H-Ras. The principal current focus of drugs entering clinic trial is inhibition of pathways downstream of activated Ras, for example, trametinib, a first-in-class MEK inhibitor. The complexity of signaling that is driven by activated Ras indicates that effective inhibition of oncogenic transduction through this approach will be difficult, with resistance being likely to emerge through switch to parallel pathways. Durable disease responses will probably require combinatorial block of several downstream targets.
Identifiers
What OpenQuestion holds
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.