Targeting histone deacetylase and NFκB signaling as a novel therapy for Mucoepidermoid Carcinomas

以组蛋白去乙酰化酶和 NFκB 信号为靶点作为粘液表皮样癌的新疗法

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作者:Vivian P Wagner, Manoela D Martins, Marco A T Martins, Luciana O Almeida, Kristy A Warner, Jacques E Nör, Cristiane H Squarize, Rogerio M Castilho

Abstract

Malignancies from the salivary glands are rare and represent 11% of all cancers from the oropharyngeal anatomical area. Mucoepidermoid Carcinomas (MEC) is the most common malignancy from the salivary glands. Low survival rates of high-grade Mucoepidermoid Carcinomas (MEC) are particularly associated with the presence of positive lymph nodes, extracapsular lymph node spread, and perineural invasion. Most recently, the presence of cancer stem cells (CSC), and the activation of the NFκB signaling pathway have been suggested as cues for an acquired resistance phenotype. We have previously shown that NFκB signaling is very active in MEC tumors. Herein, we explore the efficacy of NFκB inhibition in combination with class I and II HDAC inhibitor to deplete the population of CSC and to destroy MEC tumor cells. Our finding suggests that disruption of NFκB signaling along with the administration of HDAC inhibitors constitute an effective strategy to manage MEC tumors.

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