Evidence map›Paper›PMID 39838816›Full record

ArticleMolecular oncology2025

Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Maximilian Kramer-Drauberg, Ettore Petrini, Alessia Mira, Enrico Patrucco, Rossella Scardaci, Ilenia Savinelli, Haiyun Wang, Keying Qiao, Giovanna Carrà, Marie-Julie Nokin and 5 more

Abstract read
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In one paragraph

Article in Molecular oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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

15 authors.

Maximilian Kramer-DraubergDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy.
Ettore PetriniDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy.
Alessia MiraDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy.
Enrico PatruccoDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy.
Rossella ScardaciDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy.
Ilenia SavinelliDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy.
Haiyun WangSchool of Life Sciences and Technology, Tongji University, Shanghai, China.
Keying QiaoSchool of Life Sciences and Technology, Tongji University, Shanghai, China.
Giovanna CarràDepartment of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.ORCID https://orcid.org/0000-0002-6263-6800
Marie-Julie NokinLaboratory of Tumor and Development Biology, GIGA-Cancer, University of Liege, Belgium.
Zhiwei ZhouDepartment of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Kenneth D WestoverDepartment of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
David SantamariaMolecular Mechanisms of Cancer Program, Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Spain.
Paolo E PorporatoDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy.ORCID https://orcid.org/0000-0001-8519-1552
Chiara AmbrogioDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Italy.ORCID https://orcid.org/0000-0003-4122-701X

Funding

Associazione Italiana per la Ricerca sul CancroFondazione Umberto VeronesiGiovanni Armenise-Harvard FoundationH2020 European Research Council 101001288Justus s.s.Worldwide Cancer Research
6 · The paper itself

Abstract

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118. Our study shows for the first time the vulnerability of human mutant KRAS to oxidation, thereby paving the way to explore oxidation-based anti-KRAS treatments in humans.

Indexed as

CysteineMutationProto-Oncogene Proteins p21(ras)AnimalsCell Line, TumorHumansMiceOxidation-ReductionReactive Oxygen SpeciesCysteineKRAS protein, humanProto-Oncogene Proteins p21(ras)Reactive Oxygen Speciescysteine modificationKRAS C118NSCLConcogeneredox regulationROS

Identifiers

PMID39838816
PMCPMC11793020

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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.