Cancers, Vol. 12, Pages 756: Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid
Cancers, Vol. 12, Pages 756: Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid
Cancers doi: 10.3390/cancers12030756
Authors:
Mariah M. Hoffman
Jessica S. Zylla
Somshuvra Bhattacharya
Kristin Calar
Timothy W. Hartman
Ratan D. Bhardwaj
W. Keith Miskimins
Pilar de la Puente
Etienne Z. Gnimpieba
Shanta M. Messerli
Central nervous system atypical teratoid/rhabdoid tumors (ATRTs) are rare and aggressive tumors with a very poor prognosis. Current treatments for ATRT include resection of the tumor, followed by systemic chemotherapy and radiation therapy, which have toxic side effects for young children. Gene expression analyses of human ATRTs and normal brain samples indicate that ATRTs have aberrant expression of epigenetic markers including class I histone deacetylases (HDAC’s) and lysine demethylase (LSD1). Here, we investigate the effect of a small molecule epigenetic modulator known as Domatinostat (4SC-202), which inhibits both class I HDAC’s and Lysine Demethylase (LSD1), on ATRT cell survival and single cell heterogeneity. Our findings suggest that 4SC-202 is both cytotoxic and cytostatic to ATRT in 2D and 3D scaffold cell culture models and may target cancer stem cells. Single-cell RNA sequencing data from ATRT-06 spheroids treated with 4SC-202 have a reduced population of cells overexpressing stem...
Source: Cancers - Category: Cancer & Oncology Authors: Mariah M. Hoffman Jessica S. Zylla Somshuvra Bhattacharya Kristin Calar Timothy W. Hartman Ratan D. Bhardwaj W. Keith Miskimins Pilar de la Puente Etienne Z. Gnimpieba Shanta M. Messerli Tags: Article Source Type: research
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