ArticleProceedings of the National Academy of Sciences of the United States of America2020
An engineered chimeric toxin that cleaves activated mutant and wild-type RAS inhibits tumor growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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
27 citing papers in PubMed, 40 citations in OpenAlex.
- Engineered subtilisin protease degrades active KRAS in cancer cells leading to differential cell targeting.Research square · 2026Article
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Protein-based pan-RAS inhibitor induces tumor regression in female mice via IFNγ and CD8Nature communications · 2026Article
- Engineered subtilisin protease degrades active KRAS in cancer cells, leading to differential cell targeting.bioRxiv : the preprint server for biology · 2026Article
- Substrate specificity in a designed RAS-targeting protease is coupled to active site and distal motions.bioRxiv : the preprint server for biology · 2026Article
- ATAD2 drives melanoma growth and progression and inhibits ferroptosis.EMBO reports · 2026Article
- A nucleotide-independent, pan-RAS-targeted DARPin elicits anti-tumor activity in a multimodal manner.Molecular oncology · 2025Article
- Review
- Expression of a RAS degrader via synthetic nanocarrier-mediated mRNA delivery reduces pancreatic tumors.bioRxiv : the preprint server for biology · 2025Article
- Recent advances in targeted degradation in the RAS pathway.Future medicinal chemistry · 2025Review
- An enhanced intracellular delivery platform based on a distant diphtheria toxin homolog that evades pre-existing antitoxin antibodies.EMBO molecular medicine · 2024Article
- Structural perspectives on recent breakthrough efforts toward direct drugging of RAS and acquired resistance.Frontiers in oncology · 2024Review
- Potent and selective eradication of tumor cells by an EpCAM-targeted Ras-degrading enzyme.Molecular therapy oncolytics · 2023Article
- RAS degraders: The new frontier for RAS-driven cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Targeting Ras with protein engineering.Oncotarget · 2023Review
- Review
- Small molecular inhibitors for KRAS-mutant cancers.Frontiers in immunology · 2023Review
- Proteolytic pan-RAS Cleavage Leads to Tumor Regression in Patient-derived Pancreatic Cancer Xenografts.Molecular cancer therapeutics · 2022Article
- Targeted intracellular delivery of Cas13 and Cas9 nucleases using bacterial toxin-based platforms.Cell reports · 2022Article
- Bacterial Toxin and Effector Regulation of Intestinal Immune Signaling.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite nearly four decades of effort, broad inhibition of oncogenic RAS using small-molecule approaches has proven to be a major challenge. Here we describe the development of a pan-RAS biologic inhibitor composed of the RAS-RAP1-specific endopeptidase fused to the protein delivery machinery of diphtheria toxin. We show that this engineered chimeric toxin irreversibly cleaves and inactivates intracellular RAS at low picomolar concentrations terminating downstream signaling in receptor-bearing cells. Furthermore, we demonstrate in vivo target engagement and reduction of tumor burden in three mouse xenograft models driven by either wild-type or mutant
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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.