Abstract
Pancreatic cancer is an aggressive cancer with low survival rates. Genetic and epigenetic dysregulation has been associated with the initiation and progression of pancreatic tumors. Multiple studies have pointed to the involvement of aberrant chromatin modifications in driving tumor behavior. ATP-dependent chromatin remodeling complexes regulate chromatin structure and have critical roles in stem cell maintenance, development, and cancer. Frequent mutations and chromosomal aberrations in the genes associated with subunits of the ATP-dependent chromatin remodeling complexes have been detected in different cancer types. In this review, we summarize the current literature on the genomic alterations and mechanistic studies of the ATP-dependent chromatin remodeling complexes in pancreatic cancer. Our review is focused on the four main subfamilies: SWItch/sucrose non-fermentable (SWI/SNF), imitation SWI (ISWI), chromodomain-helicase DNA-binding protein (CHD), and INOsitol-requiring mutant 80 (INO80). Finally, we discuss potential novel treatment options that use small molecules to target these complexes.
Highlights
Pancreatic cancer is an aggressive cancer with
ATP-dependent chromatin-remodeling complexes in pancreatic cancer are limited. The scope of this to PDAC include pancreatic intraepithelial neoplasms (PanIN) and intraductal papillary mucinous review is to summarize the recent discoveries regarding the chromosomal alterations and mutations neoplasms (IPMN). Both pathways have distinct histological, genetic, and epigenetic changes associated with subunits of the ATP-dependent chromatin remodeling complexes in pancreatic cancer associated with the multistep progression from low-grade precursor lesions to high-grade precursor and discuss their mechanistic roles and their targeting as a potential treatment strategy
PDAC development is associated with precursor lesions and the two major pathways that lead to PDAC include pancreatic intraepithelial neoplasms (PanIN) and intraductal papillary mucinous neoplasms (IPMN)
Summary
Pancreatic cancer is an aggressive cancer with 80% of the patients present with an unresectable tumor [2]. Complex modifications are involved in pancreatic cancer initiation and progression. Multiple studies highlighted the involvement of epigenetic dysregulation in cancer development, progression, and chemoresistance [3,4,5,6,7,8,9]. Epigenetics are changes that result in changes of gene expression without altering the DNA sequence and involve nucleosome remodeling, histone modifications, DNA methylation, and regulation through long noncoding RNAs (Figure 1). Detailed reviews on the roles of the main subfamilies of the ATP-dependent chromatin-remodeling complexes in pancreatic cancer are limited. Cancers 2019, 11, 1859subunits of the ATP-dependent chromatin remodeling complexes in pancreatic cancer and discuss their mechanistic roles and their targeting as a potential treatment strategy
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