Evidence map›Paper›PMID 39791593›Full record

ArticleCancer medicine2025

Mutation in CDC42 Gene Set as a Response Biomarker for Immune Checkpoint Inhibitor Therapy.

Kun Wang, Yingying Zhang, Zhaoming Su, Bei Wang, Yuanyang Zhou, Xiaochu Tong, Chengying Xie, Xiaomin Luo, Sulin Zhang, Mingyue Zheng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2025. 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

10 authors.

Kun WangSchool of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Yingying ZhangSchool of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Zhaoming SuSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Bei WangSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Yuanyang ZhouDrug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Xiaochu TongDrug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Chengying XieDrug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Xiaomin LuoDrug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Sulin ZhangDrug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID https://orcid.org/0000-0002-9167-4689
Mingyue ZhengSchool of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Funding

Key Technologies R&D Program of Guangdong Province 2023B1111030004National Key Research and Development Program of China 2022YFC3400504National Natural Science Foundation of China T2225002, 82273855Natural Science Foundation of Shanghai 22ZR1474300SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program E2G805HYouth Innovation Promotion Association CAS 2023296
6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitors (ICIs) have achieved great success; however, a subset of patients exhibits no response. Consequently, there is a critical need for reliable predictive biomarkers. Our focus is on CDC42, which stimulates multiple signaling pathways promoting tumor growth. We hypothesize that an impaired function of CDC42 may serve as an indicator of a patient's response to ICI therapy.

methodsWe consider CDC42 and its downstream binding and effector proteins as a gene set, as mutations in these components could lead to defective CDC42 function. To elucidate the biomarker function of mutations within the CDC42 gene set, we curated a comprehensive discovery dataset that included seven ICI treatment cohorts. And we curated two ICI treatment cohorts for validation. We explored the mechanism based on The Cancer Genome Atlas database. We also examined whether combining a CDC42 inhibitor with ICI could enhance ICI's efficacy.

resultsMutations in the CDC42 gene set were associated with improved overall survival and progression-free survival. Furthermore, our analysis of immune response landscapes among different statuses of the CDC42 gene set supports its role as a biomarker. Animal experiments also revealed that the combination of the CDC42 inhibitor (ML141) with anti-PD-1 blockade can additively reduce tumor growth.

conclusionsOur study suggests that the CDC42 gene set mutations could potentially serve as a novel biomarker for the clinical response to ICI treatment. This finding also provides insights into the potential of combining ICI and CDC42 inhibitor use for more efficient patient treatment.

Indexed as

Biomarkers, Tumorcdc42 GTP-Binding ProteinImmune Checkpoint InhibitorsMutationAnimalsFemaleHumansMiceNeoplasmsXenograft Model Antitumor AssaysBiomarkers, Tumorcdc42 GTP-Binding ProteinCDC42 protein, humanImmune Checkpoint InhibitorsbiomarkerCDC42clinical responseimmunotherapypan‐cancer

Identifiers

PMID39791593
PMCPMC11719708

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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.