Advances in the pathogenesis and treatment of nut carcinoma: a narrative review

Abstract

NUT carcinoma (NC) is a rare, highly invasive and fatal tumor and often misdiagnosed. It typically arises from the mediastinum and midline organs and has complicated pathogenesis and poor outcome. Genetically, its pathogenesis is related to a chromosomal rearrangement involving the NUTM1 gene. In most cases, the main oncoprotein is BRD4-NUT with a translocation between NUTM1 and BRD4 genes, but in a few cases, the oncoprotein is BRD3-NUT, or NSD3-NUT. Studies have shown that the histone hyperacetylation and BRD4 hyperphosphorylation may lead to the activation of cancer circuits.Abnormal production of microRNA, inactivation of tumor suppressor genes and abnormal activation of several signaling pathways are proposed as potential mechanisms underlying the pathogenesis of NC.Currently, there is no consensus on its standard treatment for NC. Extent of surgical resection with negative margins, initial radiotherapy and part of chemotherapy regimens may significantly associated with the improvement of progression-free survival (PFS) rate and overall survival (OS) rate. Some bromodomain and extraterminal inhibitors (BETis) have shown encouraging results in the clinical trials on NC, but delayed drug resistance is still an important issue that needs to be resolved. Histone deacetylase inhibitors are also found to possess the potential in the treatment of NC. Herein, we summarize recent advances in the pathogenesis and treatment of NC.

A sinonasal NUT midline carcinoma in an 84‐year‐old man undergoing radiation and proton therapy

“…A small number undergo palliative care ( n = 3) or no treatment ( n = 1). Currently there is no established consensus on a standard treatment guideline for NMCs 2 . This case is consistent in initial presentation and tumor location with other reported head and neck NMC cases; however, the patient's age is much older than previous reported cases.…”

The contemporary management of cancers of the sinonasal tract in adults

“…These megadomains then express specific oncogenes 221–223 . There is also acetylation of p53 via this pathway (binding of p300), and thereby suppression of TP53 224 …”

“…[221][222][223] There is also acetylation of p53 via this pathway (binding of p300), and thereby suppression of TP53. 224 Unlike other head and neck cancers that have possible associations with certain environmental factors, there are currently no identified exposures (including smoking) that have been linked with NUT carcinoma. Furthermore, no link has been observed between NUT carcinoma and EBV or HPV.…”

Suspected NUT carcinoma progressing on pembrolizumab, carboplatin, and paclitaxel as first-line treatment: a case report

“…If the tumour is resectable, initial treatment often involves surgical intervention after adjuvant radiotherapy or chemotherapy. Several lines of concurrent chemotherapeutic agents have been reportedly used including cyclophosphamide, etoposide, doxorubicin, actinomycin D, vinorelbine, vinblastine, cisplatin, docetaxel, 5-fluorouracil, S1, bleomycin, vincristine, ifosfamide, gemcitabine and an uncommon treatment choice, pembrolizumab 10 . In metastatic patients or those with unresectable tumours, combination chemotherapy is highly advised followed by local management of the tumour 9 .…”