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**Chapter 5**

**Abstract**

Epigenetic Biomarkers and Their

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

**Keywords:** checkpoint, CIMP, CIN, CRC, demethylase, DNA methylation, DNMT,

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is expected to be responsible for an estimated 1.1 million deaths by 2030 [1]. With this growing global burden, prevention and treatment of CRC remains a significant public health challenge. CRC is thought to originate from sequential accumulation of genetic and epigenetic aberrations [2]. Of the identified genetic mutations, approximately 15 have been characterized as "driver mutations" and are thought to be functionally important during CRC initiation and progression [3, 4]. These include genes affecting critical cellular pathways such as those governing proliferation, apoptosis, migration, adhesion, and DNA damage and repair [3]. Importantly, it is now well established that epigenetic alterations can also serve as major driver events in the pathogenesis of CRC [5–7]. However, unlike genetic mutations, epigenetic modifications consist of heritable changes in gene expression

Therapeutic Applications in

*Antja-Voy Hartley, Matthew Martin and Tao Lu*

Colorectal Cancer

emerging avenues for future therapeutics.

**1. Introduction**

epigenetics, HAT, HDAC, methyltransferase, MSI
