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Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors

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作者：
Xu Chunwei[1,2] ; Wang Qian[3] ; Wang Dong[2] ; Wang Wenxian[4] ; Fang Wenfeng[5] ; Li Ziming[6] ; Liu Aijun[7] ; Yu Jinpu[8] ; Zhong Wenzhao[9] ; Wang Zhijie[10] ; Zhang Yongchang[11] ; Liu Jingjing[12] ; Zhang Shirong[13] ; Cai Xiuyu[14] ; Liu Anwen[15] ; Li Wen[16] ; Zhan Ping[2] ; Liu Hongbing[2] ; Lv Tangfeng[2] ; Miao Liyun[17] ; Min Lingfeng[18] ; Chen Yu[19] ; Yuan Jingping[20] ; Wang Feng[21] ; Jiang Zhansheng[22] ; Lin Gen[19] ; Huang Long[15] ; Pu Xingxiang[23] ; Lin Rongbo[19] ; Liu Weifeng[24] ; Rao Chuangzhou[25] ; Lv Dongqing[26] ; Yu Zongyang[27] ; Li Xiaoyan[28] ; Tang Chuanhao[29] ; Zhou Chengzhi[30] ; Zhang Junping[31] ; Xue Junli[32] ; Guo Hui[33] ; Chu Qian[34] ; Meng Rui[35] ; Wu Jingxun[36] ; Zhang Rui[37] ; Zhou Jin[38] ; Zhu Zhengfei[39] ; Li Yongheng[40] ; Qiu Hong[34] ; Xia Fan[39] ; Lu Yuanyuan[41] ; Chen Xiaofeng[42] ; Ge Rui[43] ; Dai Enyong[44] ; Han Yu[45] ; Pan Weiwei[46] ; Pang Fei[47] ; He Qingqing[47] ; Huang Jintao[47] ; Wang Kai[47] ; Wu Fan[48] ; Xu Bingwei[49] ; Wang Liping[50] ; Zhu Youcai[51] ; Lin Li[29] ; Xie Yanru[52] ; Lin Xinqing[30] ; Cai Jing[15] ; Xu Ling[53] ; Li Jisheng[54] ; Jiao Xiaodong[55] ; Li Kainan[56] ; Wei Jia[57] ; Feng Huijing[31] ; Wang Lin[58] ; Du Yingying[59] ; Yao Wang[60] ; Shi Xuefei[61] ; Niu Xiaomin[6] ; Yuan Dongmei[2] ; Yao Yanwen[2] ; Huang Jianhui[52] ; Feng Yue[62] ; Zhang Yinbin[63] ; Sun Pingli[64] ; Wang Hong[65] ; Ye Mingxiang[2] ; Wang Zhaofeng[2] ; Hao Yue[4] ; Wang Zhen[66] ; Wan Bin[67] ; Lv Donglai[68] ; Yang Shengjie[69] ; Kang Jin[9] ; Zhang Jiatao[9] ; Zhang Chao[9] ; Ou Juanjuan[70] ; Shi Lin[71] ; Wang Yina[72] ; Li Bihui[73] ; Zhang Zhang[74] ; Li Zhongwu[75] ; Liu Zhefeng[65] ; Yang Nong[11] ; Wu Lin[23] ; Wang Huijuan[76] ; Jin Gu[77] ; Wang Guansong[78] ; Wang Jiandong[79] ; Fang Meiyu[3] ; Fang Yong[80] ; Li Yuan[81] ; Wang Xiaojia[4] ; Zhang Yiping[4] ; Zhu Xixu[66] ; Shen Yi[82] ; Ma Shenglin[83] ; Wang Biyun[84] ; Si Lu[85] ; Song Yong[2] ; Lu Yuanzhi[86] ; Chen Jing[35,*2] ; Song Zhengbo[4,*1] ;
机构： [1]Department of Scientific Research, Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou Zhejiang, People's Republic of China. [2]Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing Jiangsu, People's Republic of China. [3]Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing Jiangsu, People's Republic of China. [4]Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, People's Republic of China. [5]Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou Guangdong, People's Republic of China. [6]Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China. [7]Senior Department of Pathology, the 7th Medical Center of PLA General Hospital, Beijing, People's Republic of China. [8]Department of Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. [9]Department of Guangdong Lung Cancer Institute, Guangdong Provincial Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, Guangzhou Guangdong, People's Republic of China. [10]State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. [11]Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha Hunan, People's Republic of China. [12]Department of Thoracic Cancer, Jilin Cancer Hospital, Jilin Changchun, People's Republic of China. [13]Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou Zhejiang, People's Republic of China. [14]Department of VIP Inpatient, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China. [15]Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang Jiangxi, People's Republic of China. [16]Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou Zhejiang, People's Republic of China. [17]Department of Respiratory Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing Jiangsu, People's Republic of China. [18]Department of Respiratory Medicine, Clinical Medical School of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou Jiangsu, People's Republic of China. [19]Department of Medical Oncology, Fujian Medical University Cancer Hospital &Fujian Cancer Hospital, Fuzhou Fujian, People's Republic of China. [20]Department of Pathology, Renmin Hospital of Wuhan University, Wuhan Hubei, People's Republic of China. [21]Department of Internal Medicine, Cancer Center of PLA, Qinhuai Medical Area, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People's Republic of China. [22]Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. [23]Department of Medical Oncology, Lung Cancer and Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha Hunan, People's Republic of China. [24]Department of Orthopaedic Oncology Surgery, Beijing Ji Shui Tan Hospital, Peking University, Beijing, People's Republic of China. [25]Department of Radiotherapy and Chemotherapy, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo Zhejiang, People's Republic of China. [26]Department of Pulmonary Medicine, Taizhou Hospital of Wenzhou Medical University, Taizhou Zhejiang, People's Republic of China. [27]Department of Respiratory Medicine, the 900th Hospital of the Joint Logistics Team (the Former Fuzhou General Hospital), Fujian Medical University, Fuzhou Fujian, People's Republic of China. [28]Department of Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China. [29]Department of Medical Oncology, Peking University International Hospital, Beijing, People's Republic of China. [30]Department of State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University (The First Affiliated Hospital of Guangzhou Medical University), Guangzhou Guangdong, People's Republic of China. [31]Department of Thoracic Oncology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan Shanxi, People's Republic of China. [32]Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. [33]Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, People's Republic of China. [34]Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, People's Republic of China. [35]Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, People's Republic of China. [36]Department of Medical Oncology, the First Affiliated Hospital of Medicine, Xiamen University, Xiamen Fujian, People's Republic of China. [37]Department of Medical Oncology, Cancer Hospital of China Medical University, Shenyang Liaoning, People's Republic of China. [38]Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology, Chengdu Sichuan, People's Republic of China. [39]Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. [40]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China. [41]Department of State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an Shaanxi, People's Republic of China. [42]Department of Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing Jiangsu, People's Republic of China. [43]Department of General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, People's Republic of China. [44]Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun Jilin, People's Republic of China. [45]Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin Heilongjiang, People's Republic of China. [46]Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing Zhejiang, People's Republic of China. [47]Department of Medical, Shanghai OrigiMed Co., Ltd., Shanghai, People's Republic of China. [48]Department of Medical, Stone Pharmaceuticals (Suzhou) Co., Ltd., Shanghai, People's Republic of China. [49]Department of Biotherapy, Cancer Institute, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China. [50]Department of Oncology, Baotou Cancer Hospital, Baotou Inner Mongolia, People's Republic of China. [51]Department of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, The Third Affiliated Hospital of Jiaxing University, Jiaxing Zhejiang, People's Republic of China. [52]Department of Oncology, Lishui Municipal Central Hospital, Lishui Zhejiang, People's Republic of China. [53]Department of Interventional Pulmonary Diseases, Anhui Chest Hospital, Hefei Anhui, People's Republic of China. [54]Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinnan Shangdong, People's Republic of China. [55]Department of Medical Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China. [56]Department of Oncology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan Shandong, People's Republic of China. [57]Department of the Comprehensive Cancer Center, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing Jiangsu, People's Republic of China. [58]Department of Pathology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan Shanxi, People's Republic of China. [59]Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei Anhui, People's Republic of China. [60]Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou Guangdong, People's Republic of China. [61]Department of Respiratory Medicine, Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Zhejiang, People's Republic of China. [62]Department of Gynecologic Radiation Oncology, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, People's Republic of China. [63]Department of Oncology, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an Shaanxi, People's Republic of China. [64]Department of Pathology, The Second Hospital of Jilin University, Changchun Jilin, People's Republic of China. [65]Senior Department of Oncology, The 5th Medical Center of PLA General Hospital, Beijing, People's Republic of China. [66]Department of Radiation Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People's Republic of China. [67]Department of Respiratory Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing Jiangsu, People's Republic of China. [68]Department of Clinical Oncology, The 901 Hospital of Joint Logistics Support Force of People Liberation Army, Hefei Anhui, People's Republic of China. [69]Department of Thoracic Surgery, Chuxiong Yi Autonomous Prefecture People's Hospital, Chuxiong, People's Republic of China. [70]Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China. [71]Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China. [72]Department of Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou Zhejiang, People's Republic of China. [73]Department of Oncology, The Second Affiliated Hospital of Guilin Medical University, Guilin Guangxi, People's Republic of China. [74]Department of International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, Guangzhou, Guangdong, People's Republic of China. [75]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China. [76]Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou Henan, People's Republic of China. [77]Department of Bone and Soft-tissue Surgery, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou Zhejiang, People's Republic of China. [78]Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China. [79]Department of Pathology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People's Republic of China. [80]Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou Zhejiang, People's Republic of China. [81]Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. [82]Department of Thoracic Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing Jiangsu, People's Republic of China. [83]Department of Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou Cancer Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou Zhejiang, People's Republic of China. [84]Department of Breast Cancer and Urological Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. [85]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China. [86]Department of Clinical Pathology, the First Affiliated Hospital of Jinan University, Guangzhou Guangdong, People's Republic of China.
出处：
DOI： 10.1055/s-0044-1781457

关键词： tyrosine receptor kinase monoclonal antibodies precision medicine targeted therapy solid tumor fusion

摘要：
The fusion genes NRG1 and NRG2 , members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1 -positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2 . Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).

基金：
This work was supported by the Natural Science Founda- tion of China (grant numbers 82002456), China Postdoc- toral Science Foundation (grant numbers 2022M723207), the Medical Scientific Research Foundation of Zhejiang Province of China (grant numbers 2023KY666), Zhejiang Traditional Chinese Medicine Science Fund Project (grant numbers 2024ZL372), Qiantang Cross Fund Project (grant numbers 2023-16), National Natural Science Foundation of China of Zhejiang Cancer Hospital Cultivation Project (grant numbers PY2023006), the Medical Scientific Research Foundation of Zhejiang Province of China (grant numbers 2024KY812), and The Natural Science Founda- tion of Zhejiang Province (grant numbers Q24H160110).
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出版当年[2023]版：
Q4 GENETICS & HEREDITY
最新[2023]版：
Q4 GENETICS & HEREDITY

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2023版]

第一作者：
第一作者机构： [1]Department of Scientific Research, Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou Zhejiang, People's Republic of China. [2]Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing Jiangsu, People's Republic of China.
共同第一作者：
通讯作者：
通讯机构： [4]Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, People's Republic of China. [35]Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, People's Republic of China. [*1]Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, People’s Republic of China [*2]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei 430022, People’s Republic of China
推荐引用方式(GB/T 7714)：
Xu Chunwei,Wang Qian,Wang Dong,et al.Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors[J].Global Medical Genetics.2024,11(01):86-99.doi:10.1055/s-0044-1781457.
APA：
Xu Chunwei,Wang Qian,Wang Dong,Wang Wenxian,Fang Wenfeng...&Song Zhengbo.(2024).Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors.Global Medical Genetics,11,(01)
MLA：
Xu Chunwei,et al."Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors".Global Medical Genetics 11..01(2024):86-99

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