Targeting Chromatin-Remodeling Factors in Cancer Cells: Promising Molecules in Cancer Therapy

Abstract

ATP-dependent chromatin-remodeling complexes can reorganize and remodel chromatin and thereby act as important regulator in various cellular processes. Based on considerable studies over the past two decades, it has been confirmed that the abnormal function of chromatin remodeling plays a pivotal role in genome reprogramming for oncogenesis in cancer development and/or resistance to cancer therapy. Recently, exciting progress has been made in the identification of genetic alteration in the genes encoding the chromatin-remodeling complexes associated with tumorigenesis, as well as in our understanding of chromatin-remodeling mechanisms in cancer biology. Here, we present preclinical evidence explaining the signaling mechanisms involving the chromatin-remodeling misregulation-induced cancer cellular processes, including DNA damage signaling, metastasis, angiogenesis, immune signaling, etc. However, even though the cumulative evidence in this field provides promising emerging molecules for therapeutic explorations in cancer, more research is needed to assess the clinical roles of these genetic cancer targets.

A novel biomarker associated with EBV infection improves response prediction of immunotherapy in gastric cancer

“…The role of CHAF1A in anti-cancer immunity remains unclear. Recently, regulators similar to CHAF1A in chromatin organization and remodeling have been reported to play critical roles in anticancer immunity, and have therefore become promising targets for cancer treatment [ 30 , 31 ]. Our GSEA showed that CHAF1A was associated with many DNA repair and metabolic pathways.…”

Gene amplification of chromatin remodeling factor SMARCC2 and low protein expression of ACTL6A are unfavorable factors in ovarian high‑grade serous carcinoma

“…There are ongoing developments in drugs that target genomic abnormalities of CRFs and combination therapies aimed at enhancing the therapeutic effects of anticancer drugs (41). In a previous study, the histone deacetylase inhibitor romidepsin, which targets CHD4, was demonstrated to suppress the progression of metastases in ovarian cancer both in vitro and in vivo (42).…”

Chromatin Remodeling-Related PRDM1 Increases Stomach Cancer Proliferation and Is Counteracted by Bromodomain Inhibitor

“…We focus on chromatin remodeling in GI cancer as it has been recently revisited as an important disease modulator and therapeutic target by us and other researchers [ 14 , 15 ]. For the storage of genetic information, chromatin is composed of the nucleosome, which contains DNA and histones [ 15 , 16 ], and for proper regulation of gene expression, nucleosomes are modulated by a chromatin remodeling complex in an ATP-dependent manner [ 16 , 17 ]. These chromatin remodeling complexes include switch/sucrose non-fermentable (SWI/SNF), initiator of SWI (ISWI), chromodomain helicase DNA binding protein (CHD), and INO80 [ 16 ], which are frequently mutated and participate in tumorigenesis in GI cancers.…”