Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two Cases
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 NUTM1 gene fusions. This article presents two unique cases of NUT sarcomas and conducts a comprehensive review of the literature to include an additi...
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Innovative Healthcare Institute
2025-03-01
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| Series: | Journal of Immunotherapy and Precision Oncology |
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| Online Access: | https://jipo.org/doi/pdf/10.36401/JIPO-24-28 |
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| author | Carlos Torrado Elise Nassif Haddad Neeta Somaiah Pavlos Msaouel Alexander J. Lazar Sarina A. Piha-Paul |
| author_facet | Carlos Torrado Elise Nassif Haddad Neeta Somaiah Pavlos Msaouel Alexander J. Lazar Sarina A. Piha-Paul |
| author_sort | Carlos Torrado |
| collection | DOAJ |
| description | 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 NUTM1 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 NUT partner genes were the MAD family in 52% of patients (33 of 63 patients, including MGA [n = 12], MXD4 [n = 12], MXD1 [n = 2], and MXI1 [n = 7]), CIC in 30% of patients (n = 19), and bromodomain (BRD) proteins in 8% of patients (n = 5 patients total, including BRD4 [n = 4] and BRD3 [n = 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 NUT 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. |
| format | Article |
| id | doaj-art-0bf4b241c094418f975f99f431d27628 |
| institution | OA Journals |
| issn | 2666-2345 2590-017X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Innovative Healthcare Institute |
| record_format | Article |
| series | Journal of Immunotherapy and Precision Oncology |
| spelling | doaj-art-0bf4b241c094418f975f99f431d276282025-08-20T02:03:07ZengInnovative Healthcare InstituteJournal of Immunotherapy and Precision Oncology2666-23452590-017X2025-03-018211312010.36401/JIPO-24-28i2590-017X-8-2-113Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two CasesCarlos Torrado0Elise Nassif Haddad1Neeta Somaiah2Pavlos Msaouel3Alexander J. Lazar4Sarina A. Piha-Paul5https://orcid.org/0000-0001-9455-16601 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA2 Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA2 Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA3 Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA4 Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA1 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USASoft tissue sarcomas (STSs) are a group of rare cancers, among which nuclear protein in testis (NUT) sarcomas represent an ultra-rare subset driven by NUTM1 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 NUT partner genes were the MAD family in 52% of patients (33 of 63 patients, including MGA [n = 12], MXD4 [n = 12], MXD1 [n = 2], and MXI1 [n = 7]), CIC in 30% of patients (n = 19), and bromodomain (BRD) proteins in 8% of patients (n = 5 patients total, including BRD4 [n = 4] and BRD3 [n = 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 NUT 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.https://jipo.org/doi/pdf/10.36401/JIPO-24-28nut sarcomacic-nutm1mad-nutm1nut fusionssarcoma |
| spellingShingle | Carlos Torrado Elise Nassif Haddad Neeta Somaiah Pavlos Msaouel Alexander J. Lazar Sarina A. Piha-Paul Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two Cases Journal of Immunotherapy and Precision Oncology nut sarcoma cic-nutm1 mad-nutm1 nut fusions sarcoma |
| title | Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two Cases |
| title_full | Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two Cases |
| title_fullStr | Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two Cases |
| title_full_unstemmed | Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two Cases |
| title_short | Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two Cases |
| title_sort | advancing understanding and therapeutic strategies for nut sarcomas comprehensive review of the literature and two cases |
| topic | nut sarcoma cic-nutm1 mad-nutm1 nut fusions sarcoma |
| url | https://jipo.org/doi/pdf/10.36401/JIPO-24-28 |
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