Signal Transduction and Targeted Therapy最新文献_第2页

Correction: Next-generation mpox vaccines: efficacy of mRNA-1769 compared to modified vaccinia virus Ankara in non-human primates

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-13 DOI: 10.1038/s41392-024-02092-9

Leonie Mayer, Leonie M. Weskamm, Marylyn M. Addo

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Clinical and biomarker analyses of SHR-1701 combined with famitinib in patients with previously treated advanced biliary tract cancer or pancreatic ductal adenocarcinoma: a phase II trial

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-13 DOI: 10.1038/s41392-024-02052-3

Lixia Yi, Haoqi Pan, Zhouyu Ning, Litao Xu, Hena Zhang, Longfei Peng, Yaowu Liu, Yifan Yang, Waimei Si, Ying Wang, Xiaoyan Zhu, Shenglin Huang, Zhiqiang Meng, Jing Xie

{"title":"Clinical and biomarker analyses of SHR-1701 combined with famitinib in patients with previously treated advanced biliary tract cancer or pancreatic ductal adenocarcinoma: a phase II trial","authors":"Lixia Yi, Haoqi Pan, Zhouyu Ning, Litao Xu, Hena Zhang, Longfei Peng, Yaowu Liu, Yifan Yang, Waimei Si, Ying Wang, Xiaoyan Zhu, Shenglin Huang, Zhiqiang Meng, Jing Xie","doi":"10.1038/s41392-024-02052-3","DOIUrl":"https://doi.org/10.1038/s41392-024-02052-3","url":null,"abstract":"Advanced biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC) have poor prognoses and limited treatment options. Here, we conducted this first-in-class phase II study to evaluate the efficacy and safety of SHR-1701, a bifunctional fusion protein targeting programmed death-ligand 1 (PD-L1) and transforming growth factor-beta (TGF-β), combined with famitinib, a multi-targeted receptor tyrosine kinase inhibitor, in patients with advanced BTC or PDAC who failed previous standard treatment (trial registration: ChiCTR2000037927). Among 51 enrolled patients, the BTC cohort showed an objective response rate (ORR) of 28% (including 2 complete responses) and a disease control rate (DCR) of 80%, with a median progression-free survival (mPFS) of 5.1 months and a median overall survival (mOS) of 16.0 months. In the PDAC cohort, the ORR was 15% (2 complete responses), with a DCR of 60%, and the mPFS and mOS were 2.1 months and 5.3 months, respectively. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 29.4% of patients, with no grade 5 TRAEs reported. Exploratory analyses revealed that primary tumor resection history, peripheral blood immunophenotype changes, and distinct immune-metabolic profiles were associated with treatment benefits. An immune/metabolism score integrating the features of six genes was developed as a predictive biomarker for immunotherapy response in multiple cohorts, allowing for the selection of patients most likely to experience positive outcomes from this therapy regimen. In conclusion, our study provides proof-of-concept data supporting the potential of SHR-1701 plus famitinib as an effective and safe subsequent-line therapy for refractory BTC and PDAC, highlighting the promise of targeting PD-L1, TGF-β, and angiogenesis pathways simultaneously.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"21 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD4 T cell contact drives macrophage cell cycle G0-G1 transition

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-13 DOI: 10.1038/s41392-024-02053-2

Petra Mlcochova, Na Zhou, Omar Shabana, Roman Fischer, Ravindra K. Gupta

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Correction: Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-11 DOI: 10.1038/s41392-024-02054-1

Han Yan, Wenjun Liu, Rui Xiang, Xin Li, Song Hou, Luzheng Xu, Lin Wang, Dong Zhao, Xingkai Liu, Guoqing Wang, Yujing Chi, Jichun Yang

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Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-11 DOI: 10.1038/s41392-024-02048-z

Sheng Li, Xiaoyou Li, Hanfeng Xu, Jiayuan Huang, Jingni Zhu, Ying Peng, Jun Bao, Liangjun Zhu

{"title":"Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial","authors":"Sheng Li, Xiaoyou Li, Hanfeng Xu, Jiayuan Huang, Jingni Zhu, Ying Peng, Jun Bao, Liangjun Zhu","doi":"10.1038/s41392-024-02048-z","DOIUrl":"https://doi.org/10.1038/s41392-024-02048-z","url":null,"abstract":"Previous studies showed encouraging efficacy of alternating FOLFOX/FOLFIRI for metastatic colorectal cancer (mCRC). This phase 2 trial (NCT04324476) aimed to evaluate efficacy and safety of alternating modified CAPOX (capecitabine and oxaliplatin)/modified CAPIRI (capecitabine and irinotecan) plus bevacizumab (anti-VEGF-A antibody) in untreated unresectable mCRC. Induction treatment included capecitabine 1000 mg/m2 bid D2–8 and D16–22, oxaliplatin 85 mg/m2 D1, irinotecan 150 mg/m2 D15, and bevacizumab 5 mg/kg D1 and 15 for 28-day cycles (up to six cycles). Capecitabine 1000 mg/m2 bid D2–15 and bevacizumab 7.5 mg/kg D1 for 21-day cycles were used as maintenance treatment. 52 patients were included. Median follow-up was 25.0 months. Median progression-free survival (PFS; the primary endpoint) was 11.0 months (95% CI 9.0–12.4). Subgroup analyses showed patients with neutrophil-to-lymphocyte ratio<5 or RAS wild-type disease had longer PFS (both P < 0.05). Objective response and disease control were obtained in 38 (73%; 95% CI 59%–84%) and 49 (94%; 95% CI 84%–99%), respectively. Mean depth of response, conversion and no evidence of disease rates were 46.0% ± 26.3%, 23% and 19%, respectively. Median overall survival was 28.1 months (18.4–34.0). Grade 3–4 treatment-related adverse events (TRAE) occurred in 17 (33%) patients. No treatment-related death was reported. The most common grade 3–4 TRAE were hypertension (13 [25%]), neutrophil count decreased (three [6%]), and hand-foot syndrome (two [4%]). In addition, grade 3–4 TRAE of diarrhea reported in one [2%] patient and no grade 3–4 peripheral neuropathy occurred. Thus, alternating modified CAPOX/CAPIRI plus bevacizumab had promising efficacy and acceptable safety. The regimen may be a novel option for untreated unresectable mCRC.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"37 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anlotinib plus chemotherapy as a first-line treatment for gastrointestinal cancer patients with unresectable liver metastases: a multicohort, multicenter, exploratory trial

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-09 DOI: 10.1038/s41392-024-02051-4

Jun-Wei Wu, Chen-Fei Zhou, Zheng-Xiang Han, Huan Zhang, Jun Yan, Jun Chen, Chun-Bin Wang, Zhi-Quan Qin, Yong Mao, Xin-Yu Tang, Liang-Jun Zhu, Xiao-Wei Wei, Dong-Hai Cui, Xiu-Li Yang, Min Shi, Li-Qin Zhao, Jin-Ling Jiang, Wei-You Zhu, Hong-Mei Wang, Chun Wang, Ling-Jun Zhu, Jun Zhang

{"title":"Anlotinib plus chemotherapy as a first-line treatment for gastrointestinal cancer patients with unresectable liver metastases: a multicohort, multicenter, exploratory trial","authors":"Jun-Wei Wu, Chen-Fei Zhou, Zheng-Xiang Han, Huan Zhang, Jun Yan, Jun Chen, Chun-Bin Wang, Zhi-Quan Qin, Yong Mao, Xin-Yu Tang, Liang-Jun Zhu, Xiao-Wei Wei, Dong-Hai Cui, Xiu-Li Yang, Min Shi, Li-Qin Zhao, Jin-Ling Jiang, Wei-You Zhu, Hong-Mei Wang, Chun Wang, Ling-Jun Zhu, Jun Zhang","doi":"10.1038/s41392-024-02051-4","DOIUrl":"https://doi.org/10.1038/s41392-024-02051-4","url":null,"abstract":"This multicohort phase II trial (ALTER-G-001; NCT05262335) aimed to assess the efficacy of first-line anlotinib plus chemotherapy for gastrointestinal (GI) cancer patients with unresectable liver metastases. Eligible patients with colorectal cancer (Cohort A) or noncolorectal and nonesophageal GI cancer (Cohort C) received six cycles of anlotinib plus standard chemotherapeutic regimens followed by anlotinib plus metronomic capecitabine as a maintenance therapy. Liver metastasectomy can be performed when liver metastases are converted to resectable lesions. The primary outcome was the investigator-confirmed objective response rate (ORR) in the intention-to-treat population. Among the 47 patients in Cohort A, the ORR was 40.4% (95% CI 26.4–55.7), including 1 with a complete response (CR) and 18 who achieved a partial response (PR). The median progression-free survival (PFS) was 8.7 months (95% CI 7.3-NE), and the median overall survival (OS) was not reached. In Cohort C, 14 of 44 patients achieved a PR, with an ORR of 31.8% (95% CI 18.6–47.6). The PFS and OS were 5.8 months (95% CI 4.8–6.5) and 11.4 months (95% CI 5.8–19.3), respectively. The liver metastasectomy rate in patients with liver-limited disease was 22.7% (5/22) in Cohort A and 6.7% (2/30) in Cohort C. For pancreatic cancer patients, the ORR of the efficacy-evaluable population was 36.0% (9/25), and those with liver-limited metastasis had better survival. Moreover, no new safety concerns emerged. In conclusion, an anlotinib-based first-line regimen demonstrated promising antitumor activity among GI cancer patients with unresectable liver metastases and led to liver metastasectomy in selected patients.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"1 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Efficacy and safety of lenvatinib plus gefitinib in lenvatinib-resistant hepatocellular carcinomas: a prospective, single-arm exploratory trial

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-09 DOI: 10.1038/s41392-024-02085-8

Yaoping Shi, Dan Cui, Lei Xia, Donghua Shi, Guangxin Jin, Siying Wang, Yan Lin, Xiaoyin Tang, Jiachang Chi, Tao Wang, Meng Li, Zicheng Lv, Jiaojiao Zheng, Qi Jia, Wu Yang, Zhen Sun, Fan Yang, Hao Feng, Shengxian Yuan, Weiping Zhou, Wenxin Qin, Rene Bernards, Haojie Jin, Bo Zhai

{"title":"Efficacy and safety of lenvatinib plus gefitinib in lenvatinib-resistant hepatocellular carcinomas: a prospective, single-arm exploratory trial","authors":"Yaoping Shi, Dan Cui, Lei Xia, Donghua Shi, Guangxin Jin, Siying Wang, Yan Lin, Xiaoyin Tang, Jiachang Chi, Tao Wang, Meng Li, Zicheng Lv, Jiaojiao Zheng, Qi Jia, Wu Yang, Zhen Sun, Fan Yang, Hao Feng, Shengxian Yuan, Weiping Zhou, Wenxin Qin, Rene Bernards, Haojie Jin, Bo Zhai","doi":"10.1038/s41392-024-02085-8","DOIUrl":"https://doi.org/10.1038/s41392-024-02085-8","url":null,"abstract":"Lenvatinib, a multi-kinase inhibitor, has been approved as first-line treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is limited. We have shown previously that lenvatinib and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) combination therapy overcomes lenvatinib resistance in HCC with high level of EGFR expression (EGFRhigh). We present here the results of a single-arm, open-label, exploratory study of lenvatinib plus the EGFR-TKI gefitinib for patients with HCC resistance to lenvatinib (NCT04642547; n = 30). Only patients with EGFRhigh HCC and progressive disease after lenvatinib treatment were recruited in the study. The most frequent adverse events of all grades were fatigue (27 patients; 90%), followed by rash (25 patients; 83.3%), diarrhea (24 patients; 80%), and anorexia (12 patients; 40%). Among 30 patients, 9 (30%) achieved a confirmed partial response and 14 (46.7%) had stable disease according to mRECIST criteria. Based on RECIST1.1, 5 (16.7%) achieved a confirmed partial response and 18 (60%) had stable disease. The estimated median progression free survival (PFS) and overall survival (OS) time were 4.4 months (95% CI: 2.5 to 5.9) and13.7 months (95% CI: 9.0 to NA), respectively. The objective response rate (ORR) of the patients in the present study compares very favorable to that seen for the two approved second line treatments for HCC (cabozantinib ORR of 4%; regorafenib ORR of 11%). Given that this combination was well-tolerated, a further clinical study of this combination is warranted.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"18 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genomic landscape of circulating tumor DNA in HER2-low metastatic breast cancer

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-09 DOI: 10.1038/s41392-024-02047-0

Zongbi Yi, Kaixiang Feng, Dan Lv, Yanfang Guan, Youcheng Shao, Fei Ma, Binghe Xu

{"title":"Genomic landscape of circulating tumor DNA in HER2-low metastatic breast cancer","authors":"Zongbi Yi, Kaixiang Feng, Dan Lv, Yanfang Guan, Youcheng Shao, Fei Ma, Binghe Xu","doi":"10.1038/s41392-024-02047-0","DOIUrl":"https://doi.org/10.1038/s41392-024-02047-0","url":null,"abstract":"The large population of HER2-low breast cancer patients necessitates further research to provide enhanced clinical guidance. In this study, we retrospectively analyzed 1071 metastatic breast cancer (MBC) patients and the circulating tumor DNA (ctDNA) to investigate clinicopathological and genetic alterations of HER2-low MBC patients. The effect of HER2-low status on different treatment modalities was explored in two prospective clinical trials (NCT03412383, NCT01917279) and a retrospective study. Our findings suggest TP53, PIK3CA, and ESR1 are frequently mutated genes in HER2-low MBC. Compared to the HER2-0 group, mutations observed in the HER2-low group are more closely associated with metabolic pathway alterations. Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group. Notably, we did not find any statistically significant disparity in the response to chemotherapy, endocrine therapy, or CDK4/6 inhibitor therapy between HER2-0 and HER2-low breast cancer patients. Interestingly, within the subgroup of individuals with metabolic pathway-related gene mutations, we found that HER2-low group exhibited a more favorable response to these treatments compared to HER2-0 group. Additionally, dynamic analysis showed the HER2-low MBC patients whose molecular tumor burden index decreased or achieved early clearance of ctDNA after the initial two treatment cycles, exhibited prolonged survival. Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"62 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular pathophysiology of Duchenne muscular dystrophy: insights from a novel rhesus macaque model

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-07 DOI: 10.1038/s41392-024-02061-2

Alessandra Moretti, Christian Kupatt, Eckhard Wolf

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Neutrophil diversity and function in health and disease

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-12-06 DOI: 10.1038/s41392-024-02049-y

Fengyuan Zhang, Yidan Xia, Jiayang Su, Fushi Quan, Hengzong Zhou, Qirong Li, Qiang Feng, Chao Lin, Dongxu Wang, Ziping Jiang

{"title":"Neutrophil diversity and function in health and disease","authors":"Fengyuan Zhang, Yidan Xia, Jiayang Su, Fushi Quan, Hengzong Zhou, Qirong Li, Qiang Feng, Chao Lin, Dongxu Wang, Ziping Jiang","doi":"10.1038/s41392-024-02049-y","DOIUrl":"https://doi.org/10.1038/s41392-024-02049-y","url":null,"abstract":"Neutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells, thereby initiating downstream signal transduction pathways. Dysfunctions in neutrophils and disruptions in neutrophil homeostasis have been implicated in the pathogenesis of numerous diseases, including cancer and inflammatory disorders, often due to aberrant intracellular signaling. This review provides a comprehensive synthesis of neutrophil biological functions, integrating recent advancements in this field. Moreover, it examines the biological roles of receptors on neutrophils and downstream signaling pathways involved in the regulation of neutrophil activity. The pathophysiology of neutrophils in numerous human diseases and emerging therapeutic approaches targeting them are also elaborated. This review also addresses the current limitations within the field of neutrophil research, highlighting critical gaps in knowledge that warrant further investigation. In summary, this review seeks to establish a comprehensive and multidimensional model of neutrophil regulation, providing new perspectives for potential clinical applications and further research.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"79 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0