Evidence map›Paper›PMID 42143039›Full record

ArticleNature communications2026

Protein-based pan-RAS inhibitor induces tumor regression in female mice via IFNγ and CD8

Teiko Komori Nomura, Kazuki Heishima, Hidefumi Mukai, Kosuke Arai, Abdelazim Elsayed Elhelaly, Hirobumi Fuchigami, Shota Warashina, Tsuyoshi Tahara, Fuminori Hyodo, Masayuki Matsuo and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Teiko Komori NomuraUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
Kazuki HeishimaCenter for One Medicine Innovative Translational Research (COMIT), Gifu University, Gifu, Japan.ORCID http://orcid.org/0000-0002-4629-8661
Hidefumi MukaiDepartment of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Kosuke AraiDepartment of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.
Abdelazim Elsayed ElhelalyDepartment of Radiology, Gifu University, Gifu, Japan.
Hirobumi FuchigamiDivision of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.ORCID http://orcid.org/0000-0001-5173-6278
Shota WarashinaDepartment of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Tsuyoshi TaharaDepartment of In vivo Imaging, Advanced Research Promoting Center, Tokushima University, Tokushima, Japan.
Fuminori HyodoCenter for One Medicine Innovative Translational Research (COMIT), Gifu University, Gifu, Japan.ORCID http://orcid.org/0000-0002-9266-9937
Masayuki MatsuoDepartment of Radiology, Gifu University, Gifu, Japan.
Masahiro YasunagaDivision of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.ORCID http://orcid.org/0000-0003-3356-0197
Kazunori AokiDepartment of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.ORCID http://orcid.org/0000-0002-1292-3764
Ryo HondaUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan. ryohonda.rh@gmail.com.ORCID http://orcid.org/0000-0003-3698-5975

Funding

Japan Agency for Medical Research and Development (AMED) 23ck0106781h0002
6 · The paper itself

Abstract

Mutations in K/H/N-RAS occur in approximately 30% of human cancers, yet most RAS mutants remain undruggable in clinical settings. Here, we describe a protein-based pan-RAS inhibitor, RRSP-RBD, that combines a RAS/Rap1A-specific endopeptidase (RRSP) with a RAS-binding domain (RBD). This engineered fusion protein localizes to RAS on the plasma membrane, where it cleaves RAS, disrupts RAS-effector interactions, and effectively inhibits downstream RAS signaling. To achieve intracellular delivery of RRSP-RBD in vivo, we engineer two cell-permeable variants. The diphtheria toxin-based version (RRSP-RBD-DTB) demonstrates femtomolar anti-tumor potency and induces tumor regression in a xenograft mouse model. The cell-permeable peptide-based version (RRSP-RBD-TAT) exhibits robust anti-tumor activity in syngeneic models without inducing irreversible toxicity in normal tissues. Interestingly, anti-tumor efficacy of RRSP-RBD-TAT critically depends on the tumor microenvironment, requiring infiltration by IFNγ

Indexed as

Antineoplastic AgentsCD8-Positive T-LymphocytesInterferon-gammaras ProteinsAnimalsCell Line, TumorDiphtheria ToxinEndopeptidasesFemaleHumansMiceMice, Inbred C57BLNecrosisRecombinant Fusion ProteinsSignal TransductionXenograft Model Antitumor AssaysAntineoplastic AgentsDiphtheria ToxinEndopeptidasesInterferon-gammaras ProteinsRecombinant Fusion Proteins

Identifiers

PMID42143039
PMCPMC13376784

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LicenceCC BY
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Registered trials

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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.