Role of Histone Deacetylases in the Pathogenesis of Salivary Gland Tumors and Therapeutic Targeting Options

Abstract

Salivary gland tumors (SGTs) comprise a rare and heterogenous category of benign/malignant neoplasms with progressively increasing knowledge of the molecular mechanisms underpinning their pathogenesis, poor prognosis, and therapeutic treatment efficacy. Emerging data are pointing toward an interplay of genetic and epigenetic factors contributing to their heterogeneity and diverse clinical phenotypes. Post-translational histone modifications such as histone acetylation/deacetylation have been shown to actively participate in the pathobiology of SGTs, further suggesting that histone deacetylating factors (HDACs), selective or pan-HDAC inhibitors (HDACis), might present effective treatment options for these neoplasms. Herein, we describe the molecular and epigenetic mechanisms underlying the pathology of the different types of SGTs, focusing on histone acetylation/deacetylation effects on gene expression as well as the progress of HDACis in SGT therapy and the current status of relevant clinical trials.

γδ T Cells: A Game Changer in the Future of Hepatocellular Carcinoma Immunotherapy

“…Epigenetic regulation plays a crucial role in the process of carcinogenesis [44][45][46][47][48]. γδ T cells, positioned at the interface of innate and adaptive immunity, exhibit a unique repertoire that necessitates in-depth investigation.…”

Drug Screening and Contrasting Sensitivities: Adenoid Cystic Carcinoma Cancer Stem Cells and Tumor Cells Differentially React to Histone Modifier Drugs

“…For example, histone deacetylase inhibitors (HDACi), a class of drugs with emerging potential for treating ACC, work by blocking the activity of histone deacetylases, enzymes responsible for removing acetyl groups from histones. By inhibiting these enzymes, changes in histones contribute to the maintenance of the stem, self-renewal, and differentiation (10,11).…”

“…For example, histone deacetylase inhibitors (HDACi), a class of drugs with emerging potential for treating ACC, work by blocking the activity of histone deacetylases, enzymes responsible for removing acetyl groups from histones. By inhibiting these enzymes, changes in histones contribute to the maintenance of the stem, self-renewal, and differentiation (10,11).Cancer stem cells (CSC), also known as tumor-initiating cells, represent a distinct subpopulation within tumors with the capacity for self-renewal and differentiation into various cell types (6, 12). These cells can exhibit a quiescent state, which makes them less susceptible to treatments that target rapidly dividing cells (5, 8).…”

Enhanced Transcriptional Signature and Expression of Histone-Modifying Enzymes in Salivary Gland Tumors

“…Although the specific etiologic factors that contribute to the development of salivary gland tumors (SGTs) are still under elucidation, there is evidence that their heterogeneity is attributed to a range of genetic alterations in addition to histopathological and morphological characteristics [4,5]. Chromosomal deletions in the 9p21 (CDKN2A gene) and 12q12-q13 (NAB2, ERBB3 genes encoding for keratins/type I and II) regions present a high incidence on subtypes of biphasic (epithelial/myoepithelial) nature, such as adenoid cystic carcinomas (ACCs) [6], and along with alterations in MYB gene expression may…”