ReviewClinical cancer research : an official journal of the American Association for Cancer Research2015
Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?
Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 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.
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.
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Who cites it
210 citing papers in PubMed, 352 citations in OpenAlex.
- KRAS is required for plexiform neurofibroma formation and represents a targetable vulnerability in established tumors.Science advances · 2026Article
- AI-Driven Multi-Omics Integration of Synthetic Colon Adenocarcinoma for Cluster-Guided PROTAC Candidate Design Targeting KRASG12D.International journal of molecular sciences · 2026Article
- KRAS G12C and KRAS G12D respond to lipid metabolism in an allele-specific manner.Journal of lipid research · 2026Article
- Rho GTPase-related prognostic signature for esophageal squamous cell carcinoma identifies CTTN as a candidate adverse prognostic marker.Molecular biology reports · 2026Article
- Temperature and lipid composition differentially regulate KRAS assemblies on membranes.Chemical communications (Cambridge, England) · 2026Article
- Crosstalk between KRAS and miRNAs in pancreatic cancer: Opportunities for its diagnosis, prognosis and therapeutic intervention (Review).International journal of oncology · 2026Review
- Targeting ICMT: A promising strategy in cancer treatment (Review).Oncology letters · 2026Review
- Review
- Targeting DNA Damage Response and Immune Crosstalk in Cancer: Mechanistic Insights and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- Wild-type RAS signaling is an essential therapeutic target inScience signaling · 2025Article
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.Biomedicines · 2025Review
- "Undruggable KRAS": druggable after all.Genes & development · 2025Review
- Emerging Targets in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Review
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- Capturing RAS oligomerization on a membrane.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- [Neurovascular pathology in a patient with neurofibromatosis type 1. Case report].Revista de neurologia · 2024Article
- Skin Development and Disease: A Molecular Perspective.Current issues in molecular biology · 2024Review
- An Improved PDE6D Inhibitor Combines with Sildenafil To InhibitJournal of medicinal chemistry · 2024Article
150 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
RAS proteins require membrane association for their biologic activity, making this association a logical target for anti-RAS therapeutics. Lipid modification of RAS proteins by a farnesyl isoprenoid is an obligate step in that association, and is an enzymatic process. Accordingly, farnesyltransferase inhibitors (FTI) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anticancer drugs was widely seen as indicating that blocking RAS membrane association was a flawed approach to cancer treatment. However, a deeper understanding of RAS modification and trafficking has revealed that this was an erroneous conclusion. In the presence of FTIs, KRAS and NRAS, which are the RAS isoforms most frequently mutated in cancer, become substrates for alternative modification, can still associate with membranes, and can still function. Thus, FTIs failed not because blocking RAS membrane association is an ineffective approach, but because FTIs failed to accomplish that task. Recent findings regarding RAS isoform trafficking and the regulation of RAS subcellular localization have rekindled interest in efforts to target these processes. In particular, improved understanding of the palmitoylation/depalmitoylation cycle that regulates RAS interaction with the plasma membrane, endomembranes, and cytosol, and of the potential importance of RAS chaperones, have led to new approaches. Efforts to validate and target other enzymatically regulated posttranslational modifications are also ongoing. In this review, we revisit lessons learned, describe the current state of the art, and highlight challenging but promising directions to achieve the goal of disrupting RAS membrane association and subcellular localization for anti-RAS drug development. Clin Cancer Res; 21(8); 1819-27. ©2015 AACR. See all articles in this CCR Focus section, "Targeting RAS-Driven Cancers."
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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.