Torrado Carlos, Nassif Haddad Elise, Somaiah Neeta, Msaouel Pavlos, Lazar Alexander J, Piha-Paul Sarina A
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Immunother Precis Oncol. 2025 Mar 5;8(2):113-120. doi: 10.36401/JIPO-24-28. eCollection 2025 May.
Soft tissue sarcomas (STSs) are a group of rare cancers, among which nuclear protein in testis (NUT) sarcomas represent an ultra-rare subset driven by gene fusions. This article presents two unique cases of NUT sarcomas and conducts a comprehensive review of the literature to include an additional 61 cases. Our review reveals that NUT sarcoma exhibits a slightly higher incidence among women (male-to-female ratio of 1:1.03) and tends to manifest at a relatively young age (median age of 40 years). The most prevalent partner genes were the family in 52% of patients (33 of 63 patients, including [ = 12], [ = 12], [ = 2], and [ = 7]), in 30% of patients ( = 19), and bromodomain (BRD) proteins in 8% of patients ( = 5 patients total, including [ = 4] and [ = 1]). Although 60% of NUT sarcomas (38 of 63 patients) are diagnosed in early stages, half of these patients (19 of 38 patients) experienced relapse despite curative-intent surgery. The median survival of the 21 patients evaluable for survival was 14 months. Finally, among 21 patients who received systemic therapy, only three patients receiving chemotherapy showed disease control, as defined by response or stability of the disease. This article emphasizes the importance of prompt diagnosis through immunohistochemistry and/or next-generation sequencing testing, advocates for the establishment of a NUT sarcoma registry, and emphasizes the need for clinical trials to advance drug development for this rare disease. Delving into a detailed analysis of pathogenesis of the distinct fusions, this article reviews innovative treatment approaches to NUT sarcoma. These strategies include BRD and extraterminal (BET) inhibitors, trabectedin, inhibitors of the EP300 histone acetyltransferase, and histone deacetylase inhibitors such as vorinostat. In the absence of clinical trials, the results from this review suggest that trabectedin-based or ifosfamide-based regimens, particularly in combination with doxorubicin, may offer a reasonable approach as frontline therapy for NUT sarcomas.
软组织肉瘤（STSs）是一组罕见癌症，其中睾丸核蛋白（NUT）肉瘤是由基因融合驱动的超罕见亚型。本文介绍了两例独特的NUT肉瘤病例，并对文献进行了全面综述，纳入另外61例病例。我们的综述显示，NUT肉瘤在女性中的发病率略高（男女比例为1:1.03），且往往在相对年轻的年龄出现（中位年龄40岁）。最常见的伙伴基因是52%的患者（63例患者中的33例，包括[ = 12]、[ = 12]、[ = 2]和[ = 7]）中的家族基因，30%的患者（ = 19）中的基因，以及8%的患者（共 = 5例患者，包括[ = 4]和[ = 1]）中的溴结构域（BRD）蛋白。尽管60%的NUT肉瘤（63例患者中的38例）在早期被诊断出，但这些患者中有一半（38例患者中的19例）尽管接受了根治性手术仍出现复发。可评估生存情况的21例患者的中位生存期为14个月。最后，在接受全身治疗的21例患者中，只有3例接受化疗的患者显示疾病得到控制，疾病控制定义为疾病缓解或稳定。本文强调通过免疫组织化学和/或下一代测序检测进行快速诊断的重要性，主张建立NUT肉瘤登记处，并强调需要开展临床试验以推进针对这种罕见疾病的药物研发。深入详细分析不同融合的发病机制后，本文综述了NUT肉瘤的创新治疗方法。这些策略包括BRD和末端外（BET）抑制剂、曲贝替定、EP300组蛋白乙酰转移酶抑制剂以及诸如伏立诺他等组蛋白去乙酰化酶抑制剂。在缺乏临床试验的情况下，本综述结果表明，基于曲贝替定或基于异环磷酰胺的方案，特别是与多柔比星联合使用时，可能作为NUT肉瘤一线治疗的合理方法。
