ReviewNature reviews. Drug discovery2014
Drugging the undruggable RAS: Mission possible?
Review in Nature reviews. Drug discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07004244 (Safety and Efficacy of KRAS Vaccine in the Treatment of KRAS-mutant Malignancies), which is not on this map. Cited by 1,101 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Safety and Efficacy of KRAS Vaccine in the Treatment of KRAS-mutant Malignancies
Who cites it
1,101 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,963 citations in OpenAlex.
- Efficacy and toxicity of KRASWorld journal of surgical oncology · 2024Pooled it
- KRAS-G12D inhibitor HRS-4642 plus chemotherapy in advanced KRASNature medicine · 2026Trial
- Safety and efficacy of lapatinib, binimetinib, and vinorelbine for RAS mutant metastatic colorectal cancer: results of the RASTRIC Phase I/II trial.British journal of cancer · 2026Trial
- Trial
- Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.Cancer biology & therapy · 2026Review
- Design, synthesis and biological evaluation of novel KRAS-G12D inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Article
- Activity and specificity of KRAS variants-directed Revolution Medicines Company (RMC) compounds for pleural effusion-derived non-small cell lung cancer cell lines.Translational lung cancer research · 2026Article
- Engineered subtilisin protease degrades active KRAS in cancer cells leading to differential cell targeting.Research square · 2026Article
- Beyond KRASG12C: emerging therapeutic strategies, patent landscape, and clinical progress in targeting KRAS-mutant cancers.Medical oncology (Northwood, London, England) · 2026Review
- Beyond KRASG12C: emerging therapeutic strategies, patent landscape, and clinical progress in targeting KRAS-mutant cancers.Medical oncology (Northwood, London, England) · 2026Review
- HRAS promotes mutant NRAS-driven transformation with codon and allele specificity.Science signaling · 2026Article
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026Review
- Similarity-Enhanced Representation Learning of Non-Canonical Amino Acids for Therapeutic Peptide Modeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Computational identification and characterization of high-risk human KRAS nsSNPs: Impacting structure, ligand binding, and cancer prognosis.Journal, genetic engineering & biotechnology · 2026Article
- Invasive mucinous adenocarcinoma of the lung: integrating molecular landscape, imaging phenotypes, and translational therapeutic strategies.Translational lung cancer research · 2026Review
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- Craspase Protease Activation Is Sensitive to Oncogenic Single-Nucleotide RNA Mismatches.ACS chemical biology · 2026Article
- Targeted KRASG12V Degradation In Vivo Elicits Lung Adenocarcinoma Regression with Subsequent Relapse from Dysregulated Proteolysis.Cancer research · 2026Article
1,041 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Despite more than three decades of intensive effort, no effective pharmacological inhibitors of the RAS oncoproteins have reached the clinic, prompting the widely held perception that RAS proteins are 'undruggable'. However, recent data from the laboratory and the clinic have renewed our hope for the development of RAS-inhibitory molecules. In this Review, we summarize the progress and the promise of five key approaches. Firstly, we focus on the prospects of using direct inhibitors of RAS. Secondly, we address the issue of whether blocking RAS membrane association is a viable approach. Thirdly, we assess the status of targeting RAS downstream effector signalling, which is arguably the most favourable current approach. Fourthly, we address whether the search for synthetic lethal interactors of mutant RAS still holds promise. Finally, RAS-mediated changes in cell metabolism have recently been described and we discuss whether these changes could be exploited for new therapeutic directions. We conclude with perspectives on how additional complexities, which are not yet fully understood, may affect each of these approaches.
Indexed as
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.