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Review
. 2025 Jul 31;7(1):101068.
doi: 10.1016/j.xinn.2025.101068. eCollection 2026 Jan 5.

International guidelines on the diagnosis and treatment of NUT carcinoma

Yu Zhang  1 Qi Zhang  1 Yue Hao  2 Jia Luo  3 Yingshi Piao  4 Wenxian Wang  2 Zhengbo Song  2 Ziming Li  5 Luka Brcic  6 Aijun Liu  7 Jinpu Yu  8 Yasuhiro Tsutani  9 Wenzhao Zhong  10 Wenfeng Fang  11 Zhijie Wang  12 Shengxiang Ren  13 Athanasios G Papavassiliou  14 Yongchang Zhang  15 Jingjing Liu  16 Shirong Zhang  17 Xiuyu Cai  18 Ayten Kayi Cangir  19 Anwen Liu  20 Wen Li  21 Filippo Lococo  22 Ping Zhan  23 Hongbing Liu  23 Tangfeng Lv  23 Liyun Miao  24 Lingfeng Min  25 Helmut Popper  26 Yu Chen  27 Jingping Yuan  28 Feng Wang  29 Zhansheng Jiang  30 Gen Lin  27 Long Huang  20 Xingxiang Pu  31 Rongbo Lin  27 Kalevi Kairemo  32 Weifeng Liu  33 Chuangzhou Rao  34 Dongqing Lv  35 Zongyang Yu  36 Ashrafian Leanne  37 Xiaoyan Li  38 Chuanhao Tang  39 Hifzur R Siddique  40 Chengzhi Zhou  41 Junping Zhang  42 Junli Xue  43 Vishal Shelat  44 Hui Guo  45 Qian Chu  46 Rui Meng  47 Fatemeh Ardeshir  48 Jingxun Wu  49 Rui Zhang  50 Jin Zhou  51 Robert A Kratzke  52   53 Zhengfei Zhu  54 Yongheng Li  55 Hong Qiu  46 Fan Xia  54 Fiorella Calabrese  56 Yang Xia  21 Alessandro Wasum Mariani  57 Yuanyuan Lu  58 Xiaofeng Chen  59 Mark A Klein  60   61 Rui Ge  62 Enyong Dai  63 Axel H Schönthal  64 Yu Han  65 Zhenying Guo  66 Jian Zhang  67 Yinghua Ji  68 Xianbin Liang  69 Hongmei Zhang  70 Xuelei Ma  71 Marco Chiappetta  72 Xuewen Liu  73 Francoise Galateau Salle  74 Yu Yao  75 Malgorzata Szolkowska  76 Weiwei Pan  77 Fei Pang  78 Fan Wu  79 Stefan B Watzka  80 Liping Wang  81 Youcai Zhu  82 Li Lin  39 Aparna Sharma  83 Jianfei Tu  84 Xinqing Lin  41 Jing Cai  20 Ling Xu  85 Jisheng Li  86 Xiaodong Jiao  87 Kainan Li  88 Marjorie G Zauderer  89   90 Jia Wei  91 Huijing Feng  42 Lin Wang  92 Yingying Du  93 Wang Yao  94 Elizabeth Dudnik  95 Xuefei Shi  96 Xiaomin Niu  5 Dongmei Yuan  23 Yanwen Yao  23 Jianhui Huang  84 Yue Feng  97 Yinbin Zhang  45 Binbin Song  98 Wenfeng Li  99 Jianfei Fu  100 Marina K Baine  101 Pingli Sun  102 Hong Wang  103 Mingxiang Ye  23 Dong Wang  23 Zhaofeng Wang  23 Jing Wu  1 Yunyun Yang  4 Yuan Fang  104 Zhen Wang  105 Bin Wan  106 Donglai Lv  107 Huafei Chen  82 Shengjie Yang  108 Jing Kang  10 Jiatao Zhang  10 Chao Zhang  10 Lin Shi  109 Yina Wang  110 Mohamed Emam Sobeih  111 Bihui Li  112 Bin Lian  113 Lili Mao  113 Zhang Zhang  114 Ke Wang  115   116 Zhongwu Li  117 Zhefeng Liu  103 Nong Yang  15 Lin Wu  31 Xiaobing Chen  118 Gu Jin  119 Miao Li  120 Guansong Wang  121 Thomas U Marron  122 Jiandong Wang  123 Sanjay Popat  124 Meiyu Fang  2 Yong Fang  125 Daniel Mansilla  126 Yuan Li  127 Xiaojia Wang  2 Jing Chen  47 Yiping Zhang  2 Xixu Zhu  105 Yi Shen  128 Shenglin Ma  129 Aaron S Mansfield  130 Biyun Wang  131 Lu Si  113 Anja C Roden  132 Bjørn H Grønberg  133   134 Yong Song  23 Geoffrey I Shapiro  135   136   137 Christopher A French  138 Yuanzhi Lu  139 Qian Wang  140 Chunwei Xu  141
Affiliations
Review

International guidelines on the diagnosis and treatment of NUT carcinoma

Yu Zhang et al. Innovation (Camb). .

Abstract

Nuclear protein in testis (NUT) carcinoma (NC) represents a rare, clinically aggressive cancer defined by pathognomonic NUT Midline Carcinoma Family Member 1 (NUTM1) gene fusions, with bromodomain and extraterminal domain (BET) protein 4 (BRD4)-NUTM1 being the predominant oncogenic driver. Since its description in 1991, gradual advances have clarified the pathologic mechanisms of NC and its diagnostic methods; however, NC treatment remains a significant challenge. Moreover, diagnostic and treatment approaches for this cancer require further validation and standardization. These guidelines were developed by the Chinese Alliance of Research for NC (ChARN) based on current evidence in the literature and incorporate consensus-based input from multiple international experts. They provide comprehensive guidance on NC diagnosis and treatment, covering epidemiology, pathogenesis, diagnostic methods, therapeutic strategies, BET-inhibitor toxicity, palliative care, and prognostic assessment during follow-up. They also emphasize the importance of multidisciplinary team collaboration in NC treatment and recommend prioritizing enrollment in prospective clinical trials for patients. Current mainstays of treatment include surgical resection, radiotherapy, and medical treatment (chemotherapy, targeted therapy, and immunotherapy), although no standard treatment protocol exists. Future research directions include improving diagnostic efficiency, exploring new therapeutic strategies (such as highly selective BET inhibitors, BET-inhibitor combinations, and PROTAC technologies), and recommending basket trials as a research approach for patients with NUTM1 gene fusions.

Keywords: NUT carcinoma; diagnosis; guideline; treatment.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Pathogenic mechanisms of NUT-fusion oncoprotein
Figure 2
Figure 2
NUT diagnostic and treatment flowchart

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