Luo Jia, Bishop Justin A, DuBois Steven G, Hanna Glenn J, Sholl Lynette M, Stelow Edward B, Thompson Lester D R, Shapiro Geoffrey I, French Christopher A
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Rev Clin Oncol. 2025 Apr;22(4):292-306. doi: 10.1038/s41571-025-00986-3. Epub 2025 Feb 3.
In the past two decades, treatment for non-small-cell lung cancers (NSCLCs) and head and neck squamous cell carcinoma (HNSCC) has advanced considerably, owing largely to the characterization of distinct oncological subtypes, the development of targeted therapies for each subtype and the advent of immunotherapy. Data emerging over the past two decades suggest that NUT carcinoma, a highly aggressive malignancy driven by a NUT fusion oncoprotein and arising in the lungs, head and neck, and rarely in other sites, is a squamous cell carcinoma (SCC) based on transcriptional, histopathological, cell-of-origin and molecular characteristics. NUT carcinoma has an estimated incidence of 1,400 cases per year in the United States, surpassing that of some rare NSCLC and HNSCC subtypes. However, NUT carcinoma is currently not recognized as an SCC of the lungs or head and neck. The orphan classification of NUT carcinoma as a distinct entity leads to a lack of awareness of this malignancy among oncologists and surgeons, despite early diagnosis being crucial for this cancer type with a median survival of only ~6.5 months. Consequently, NUT carcinoma is underdiagnosed and often misdiagnosed, resulting in limited research and progress in developing effective treatments in one of the most aggressive forms of lung and head and neck cancer. With a growing number of targeted agents that can potentially be used to treat NUT carcinoma, improved recognition through reclassification and inclusion of NUT carcinoma as a squamous NSCLC or an HNSCC when arising in these locations will accelerate the development of effective therapies for this disease. Thus, in the Perspective, we propose such a reclassification of NUT carcinoma as an SCC and discuss the supporting evidence.
在过去二十年中，非小细胞肺癌（NSCLC）和头颈部鳞状细胞癌（HNSCC）的治疗取得了显著进展，这在很大程度上归功于不同肿瘤亚型的特征描述、针对每种亚型的靶向治疗的发展以及免疫疗法的出现。过去二十年出现的数据表明，NUT癌是一种高度侵袭性的恶性肿瘤，由NUT融合癌蛋白驱动，发生于肺、头颈部，很少见于其他部位，根据转录、组织病理学、起源细胞和分子特征，它是一种鳞状细胞癌（SCC）。在美国，NUT癌的估计发病率为每年1400例，超过了一些罕见的NSCLC和HNSCC亚型。然而，NUT癌目前未被认定为肺或头颈部的SCC。将NUT癌作为一种独特实体进行罕见病分类，导致肿瘤学家和外科医生对这种恶性肿瘤缺乏认识，尽管早期诊断对这种癌症类型至关重要，其中位生存期仅约6.5个月。因此，NUT癌诊断不足且常被误诊，导致在这种最具侵袭性的肺癌和头颈部癌之一的有效治疗开发方面研究有限且进展缓慢。随着越来越多的靶向药物可能用于治疗NUT癌，通过重新分类提高认识，并在NUT癌发生于这些部位时将其纳入鳞状NSCLC或HNSCC，将加速针对该疾病的有效疗法的开发。因此，在这篇观点文章中，我们提议将NUT癌重新分类为SCC并讨论支持证据。
