Mutation in CDC42 Gene Set as a Response Biomarker for Immune Checkpoint Inhibitor Therapy
文献类型：期刊论文
| 作者 | Wang, Kun3,4,5; Zhang, Yingying3,4,5; Su, Zhaoming2; Wang, Bei2; Zhou, Yuanyang3; Tong, Xiaochu3; Xie, Chengying1,3 ; Luo, Xiaomin3; Zhang, Sulin3; Zheng, Mingyue2,3,4,5
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| 刊名 | CANCER MEDICINE
 |
| 出版日期 | 2025 |
| 卷号 | 14期号:1页码:13 |
| 关键词 | biomarker CDC42 clinical response immunotherapy pan-cancer |
| ISSN号 | 2045-7634 |
| DOI | 10.1002/cam4.70556 |
| 英文摘要 | 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. |
| WOS关键词 | CTLA-4 BLOCKADE ; CELL ; SENSITIVITY ; RESISTANCE ; LANDSCAPE |
| 资助项目 | Youth Innovation Promotion Association CAS[1965-2022] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:001393811700001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315645]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Sulin; Zheng, Mingyue |
| 作者单位 | 1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China 4.Univ Sci & Technol China, USTC, Affiliated Hosp 1, Anhui Prov Hosp,Div Life Sci & Med, Hefei, Peoples R China 5.Univ Sci & Technol China, Sch Life Sci, Div Life Sci & Med, Hefei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Kun,Zhang, Yingying,Su, Zhaoming,et al. Mutation in CDC42 Gene Set as a Response Biomarker for Immune Checkpoint Inhibitor Therapy[J]. CANCER MEDICINE,2025,14(1):13. |
| APA | Wang, Kun.,Zhang, Yingying.,Su, Zhaoming.,Wang, Bei.,Zhou, Yuanyang.,...&Zheng, Mingyue.(2025).Mutation in CDC42 Gene Set as a Response Biomarker for Immune Checkpoint Inhibitor Therapy.CANCER MEDICINE,14(1),13. |
| MLA | Wang, Kun,et al."Mutation in CDC42 Gene Set as a Response Biomarker for Immune Checkpoint Inhibitor Therapy".CANCER MEDICINE 14.1(2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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