International Journal of Molecular Medical Science, 2024, Vol.14, No.4, 227-238 http://medscipublisher.com/index.php/ijmms 228 disease typically progresses through a series of well-defined stages, starting from benign adenomas to malignant adenocarcinomas, driven by both genetic and epigenetic alterations (Sharma et al., 2010; Jung et al., 2020). The global burden of CRC is substantial, with variations in incidence and mortality rates observed across different regions, influenced by factors such as diet, lifestyle, and genetic predisposition (Jung et al., 2020). 2.2 Pathogenesis and progression of colon cancer The pathogenesis of colon cancer involves a complex interplay of genetic mutations and epigenetic modifications. Genetic alterations, such as mutations in oncogenes and tumor suppressor genes, play a crucial role in the initiation and progression of CRC. However, epigenetic changes, including DNA methylation, histone modifications, and non-coding RNA regulation, are equally important in driving the disease (Sharma et al., 2010; Dawson and Kouzarides, 2012; Jung et al., 2020). DNA methylation, in particular, has been extensively studied and is known to contribute to the silencing of tumor suppressor genes, thereby promoting tumorigenesis (Lay et al., 2015; Skvortsova et al., 2019). These epigenetic changes are not only pivotal in the early stages of CRC but also in its progression to more advanced stages (Nebbioso et al., 2018; Jung et al., 2020). 2.3 Current diagnostic and therapeutic strategies The diagnosis and treatment of colon cancer have evolved significantly with advancements in our understanding of its molecular underpinnings. Traditional diagnostic methods, such as colonoscopy and histopathological examination, are now complemented by molecular biomarkers that can provide insights into the epigenetic landscape of CRC (Watanabe and Maekawa, 2010; Jung et al., 2020). DNA methylation markers, for instance, have been commercialized and are used in clinical practice for early detection and prognostication (Toiyama et al., 2014; Jung et al., 2020). Therapeutically, the management of CRC includes surgical resection, chemotherapy, and radiation therapy. However, the emergence of epigenetic therapies offers new avenues for treatment. Epigenetic drugs, such as DNA methyltransferase inhibitors and histone deacetylase inhibitors, have shown promise in preclinical and clinical studies, highlighting the potential of targeting epigenetic modifications to improve patient outcomes (Sharma et al., 2010; Dawson and Kouzarides, 2012; Nebbioso et al., 2018). The integration of these novel therapies into clinical practice is expected to enhance the precision and efficacy of CRC treatment, ushering in an era of personalized medicine (Sharma et al., 2010; Dawson and Kouzarides, 2012; Jung et al., 2020). The comprehensive understanding of the epigenetic landscape of colon cancer has not only provided valuable insights into its pathogenesis and progression but also paved the way for innovative diagnostic and therapeutic strategies that hold promise for improving patient care and outcomes. 3 Epigenetics in Cancer 3.1 Definition and key concepts Epigenetics refers to heritable changes in gene expression that do not involve alterations to the underlying DNA sequence. These changes can affect how cells read genes and are crucial for normal development and cellular differentiation. In the context of cancer, epigenetic modifications can lead to the activation of oncogenes or the silencing of tumor suppressor genes, contributing to malignant transformation and tumor progression (Sharma et al., 2010; Berdasco and Esteller, 2010; Kelly and Issa, 2017). 3.2 Major epigenetic mechanisms 3.2.1 DNA methylation DNA methylation involves the addition of a methyl group to the 5' position of cytosine residues in CpG dinucleotides, leading to gene silencing. Aberrant DNA methylation patterns are a hallmark of cancer and can result in the inactivation of tumor suppressor genes and the activation of oncogenes. In colorectal cancer (CRC), for instance, DNA methylation changes are prevalent and have been developed as biomarkers for diagnosis and prognosis (Okugawa et al., 2015; Jung et al., 2020).
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