In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3990-3990
Abstract:
Purpose: NUT midline carcinoma (NMC) is an aggressive and poorly differentiated carcinoma defined by chromosomal rearrangements of NUT gene, which is fused to the BET family genes (BRD3/4). Although NMC is extremely rare and mostly reported in a Western population, clinico-pathologic findings of Asian NMC patients are not well studied. Here, we performed the clinicopathologic analysis of Korean NMC cases and in vitro efficacy of MYC-targeting agents against patient-derived NMC cell lines. Experimental Design: A total of 12 NMC patients (3 thoracic and 9 head and neck origins) were collected in Korean multi-centers by immunohistochemistry (IHC) and fluorescence in situ hybridization for NUT. IHC staining was performed for c-MYC, p53, EGFR, HER2, and PD-L1. NMC cell lines (SNU-2972-1, SNU-3178S, HCC2429, and Ty-82) were exposed to MYC-targeting agents including BET (I-BET, OTX-015, and AZD5153) and HDAC (vorinostat, romidepsin, panobinostat, and CUDC-907) inhibitors. Cell viability assays were performed and IC50 values were determined. Results: Primary sites of tumor included sinonasal area (n=7), salivary gland (n=2), and thorax/lung (n=3). The median age was 47.5 years (range, 8-73 years) with equal male-to-female ratio. NUT immunostaining showed diffuse positivity in all except for one who had focal NUT positivity. C-MYC and p53 were expressed in all evaluated cases. PD-L1 expression was observed only in a patient (8.3%). Seven of 12 patients died at 3-24 months (median, 9 months) after diagnosis. Long-term survivor was observed in one patient with stage IV NMC who received mass excision plus metastasectomy followed by 6 cycles of docetaxel plus cisplatin and radiotherapy (survival & gt; 27 months). Although BET and HDAC inhibitors showed limited in vitro efficacies against NMC cells, a dual HDAC/PI3K inhibitor, CDUC-907 exhibited the most potent efficacy with the IC50 of 6.2 to 9 pmol/L. Conclusions: Korean NMC patients pursued grave prognosis like Western patients except one long-term survivor who received tri-modality treatments. Dual HDAC/PI3K inhibitor might be promising in NMC treatment. Citation Format: Soyeon Kim, Minsun Jung, Heae Surng Park, Sun Och Yoon, Soon Won Hong, Weon-Seo Park, Bhumsuk Keam, Hyun Jik Kim, Dong-Wan Kim, Young Tae Kim, Dae Seong Heo, Tae Min Kim, Yoon Kyung Jeon. Clinicopathologic findings and in vitro efficacy of MYC-targeting agentsin NUT midline carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3990.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2018-3990
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
Permalink
