Epigenetic Biomarkers and Their Therapeutic Applications in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most aggressive cancers worldwide and is known to develop through a stepwise process involving the accumulation of several genetic and epigenetic alterations. Furthermore, numerous studies have highlighted the significant role that certain epigenetic enzymes play in CRC pathogenesis, particularly those that govern chromatin components in the promoter regions of tumor suppressors and oncogenes. Here, we delineate the relationship between CRC-associated epigenetic marks, their modifying enzymes, and the classification of CRC into distinct molecular pathways or subtypes. Moreover, we discuss some of the most prominent methyltransferases, demethylases, acetyltransferases, and deacetylases, which have been targeted for preclinical and clinical CRC treatment. Notably, inhibitors against these epigenetic enzymes are a promising new class of anticancer drugs, with several obtaining Food and Drug Administration (FDA) approval for the treatment of blood and solid tumors. By highlighting the epigenetic molecular pathways leading to CRC development as well as providing an update on current CRC epigenetic therapies, this chapter sheds fresh insight into new and emerging avenues for future therapeutics.

Detecting colorectal cancer using genetic and epigenetic biomarkers: screening and diagnosis

“…During the onset of cancer, hypermethylation in the promoter region may result in the inactivation of tumor-suppressor genes, whereas global hypomethylation is linked to genomic instability and chromosomal abnormalities [ 70 ]. While hypomethylation is a gradually early event in tumor progression, hypermethylation accumulates in more advanced stages [ 69 , 78 ]. Blood and stool-based CRC DNA methylation indicators have exhibited sensitivities between 90-95% and specificities between 85-95% [ 79 ].…”

“…Numerous studies highlight the significant role of histone modification in the development of CRC [ 111 ], indicating its potential as a biomarker for the disease [ 112 – 114 ]. The two histone aberrations most frequently studied in CRC are histone acetylation and methylation [ 69 , 115 ].…”