clinicopathological and preclinical findings of nut carcinoma a multicenter study background nut carcinoma is a rare aggressive disease caused by brd43nut fusion and cmyc upregulation plays a key role in the pathogenesis here we report on the clinicopathological characteristics of korean patients with nut carcinoma and the in vitro efficacy of myctargeting agents against patientderived nut carcinoma cell linesmaterials and methods thirteen patients with nut carcinoma were evaluated for p53 cmyc epidermal growth factor receptor egfr her2 and programmed cell death ligand 1 pdl1 by immunohistochemistry the half maximal inhibitory concentration ic50 values of nut carcinoma cell lines snu29721 snu3178s hcc2429 and ty82 were determined using myctargeting agents including bromodomain and extraterminal bet inhibitors ibet otx015 azd5153 and histone deacetylase hdac inhibitors vorinostat romidepsin panobinostat cudc907results primary tumor sites included head and neck n 9 and lung n 4 the patient age ranged from 8 to 73 years with the malefemale ratio of 121 nine patients died at 3236 months median 106 after diagnosis eight patients had been misdiagnosed initially with other diseases one patient with metastatic nut carcinoma who received mass excision plus metastasectomy followed by chemoradiotherapy was a longterm survivor 27 months although expressions of cmyc 812 73 and p53 1212 100 were commonly observed egfr her2 and pdl1 expressions were observed in 2 of 7 29 2 of 8 25 and 1 of 12 83 patients respectively bet and hdac inhibitors showed variable but limited in vitro efficacy however a dual hdacpi3k inhibitor cudc907 was most potent against nut carcinoma cells with an ic50 of 5590 pmoll consistent with these findings kinome short interfering rna screening showed a positive hit for pi3kca in nut carcinoma cells panobinostat ic50 0413 nmoll and a bivalent bet inhibitor azd5153 ic50 3782 nmoll also showed remarkable efficaciesconclusion east asian patients with nut carcinoma showed dismal survival outcomes like western patients and cudc907 might be promising in nut carcinoma treatmentimplications for practice nut carcinoma nc is a disease caused by brdnut fusion leading to cmyc upregulation nc is often misdiagnosed and very aggressive requiring development of effective therapeutic strategy this article presents the clinicopathological features of the largest series of ncs in east asians and preclinical sensitivities to myctargeting agents in nc cell lines patients with nc had grave outcomes and poor response to treatment among myctargeting agents including bet and hdac inhibitors cudc907 a dual pi3khdac inhibitor was most effective against nc cells followed by panobinostat an hdac inhibitor and azd5153 a bivalent bet inhibitor cudc907 might be promising in nc treatment