Ye Zhuomiao, Li Xin, Zhang Minghui, Xie Fei, Luo Xiangwen, Deng Chao, Yang Dan, Yin Mingzhu
Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC), and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, Wanzhou District, Chongqing, People's Republic of China.
Institute of Advanced Interdisciplinary Studies, Chongqing University, Chongqing, People's Republic of China.
JTO Clin Res Rep. 2025 Aug 5;6(10):100885. doi: 10.1016/j.jtocrr.2025.100885. eCollection 2025 Oct.
NUT carcinoma is a rare and highly aggressive malignancy characterized by rapid progression, resistance to conventional therapies, and an extremely poor prognosis. This report presents a 36-year-old patient with stage IIIB primary pulmonary NUT carcinoma who achieved remarkable clinical outcomes with NHWD-870 monotherapy, a novel BET inhibitor. After just 1 month of treatment, imaging revealed a partial response, and a complete response was achieved within 5 months. Postoperative pathologic examination confirmed no residual cancer cells, and the patient has remained disease-free without recurrence or metastasis to date. To explore the underlying mechanisms of this therapeutic response, single-cell RNA sequencing was performed on the tumor tissue, revealing enhanced activity of immune cells, particularly effector CD8+ T-cells, within the tumor microenvironment. This suggests that NHWD-870 exerts its effects through both direct tumor suppression and modulation of the immune microenvironment. This case highlights the exceptional efficacy of BET inhibitors in the treatment of NUT carcinoma, as evidenced by the first report of complete response achieved with BET inhibitor monotherapy, and supports their potential as a personalized therapeutic strategy.
NUT癌是一种罕见且侵袭性极强的恶性肿瘤，其特点是进展迅速、对传统疗法耐药且预后极差。本报告介绍了一名36岁的IIIB期原发性肺NUT癌患者，该患者使用新型BET抑制剂NHWD - 870单药治疗取得了显著的临床疗效。治疗仅1个月后，影像学检查显示部分缓解，5个月内实现了完全缓解。术后病理检查证实无残留癌细胞，患者至今无疾病复发或转移，一直处于无病状态。为探究这种治疗反应的潜在机制，对肿瘤组织进行了单细胞RNA测序，结果显示肿瘤微环境中免疫细胞，尤其是效应性CD8 + T细胞的活性增强。这表明NHWD - 870通过直接抑制肿瘤和调节免疫微环境发挥作用。该病例突出了BET抑制剂在治疗NUT癌方面的卓越疗效，这是BET抑制剂单药治疗实现完全缓解的首例报告所证明的，并支持了其作为个性化治疗策略的潜力。
