Chromosomes were first identified as carriers of genetic information in 1902 (Satzinger, 2008) and later characterized as comprised of DNA and histone proteins and considered genome units (Goldman and Landweber, 2016, Watson and Crick, 1953). Even though all the cells in the body have the same genome, each cell has specific physiological functions. Such phenotypic diversity can be achieved through protein, RNA, and DNA regulation. Changes at the epigenetic (“Epi” in Greek means “beyond” or “above”) level also contribute to this variety of phenotypes (Kilpinen & Dermitzakis, 2012). The conceptualization of epigenetics was initiated by Conrad Waddington, who studied how genotypes can give rise to phenotypes during development (Waddington, 1957). At the molecular level, the epigenome consists of chemical compounds that modify DNA sequences or chromosome structures, resulting in an added layer of complexity in gene expression and phenotypic changes (Bird, 2007, Black et al., 2012, Miranda and Jones, 2007, Weber and Schubeler, 2007). Epigenetic changes are reversible and do not change the underlying DNA sequence. However, they can also persist through cell division and can be inherited over multiple generations (Bird, 2007, Cubas et al., 1999). Dysregulation of the epigenome as well as genome can contribute to cancer development and progression (Feinberg and Vogelstein, 1983, Hsu et al., 1991).

Cancer is a major public health burden, with 10 million cancer-related deaths in 2020 (Sung et al., 2021). The past few years have seen major advances in understanding the epigenome and its relation to cancer. The epigenome is often dysregulated in cancers (Marini et al., 2006, Mirmohammadsadegh et al., 2006, Richter et al., 2020, Yu et al., 2020). These epigenetic alterations can be induced by various environmental factors such as smoking, diet, and carcinogen exposure, which can contribute to the transformed phenotype of cancer cells by silencing tumor suppressor genes and/or activating oncogenes. For example, aberrant changes in the epigenome (both DNA and histones) that activate oncogenes and inhibit tumor suppressors can lead to cancer (Marini et al., 2006, Mirmohammadsadegh et al., 2006, Richter et al., 2020, Yu et al., 2020). In addition, it has been reported that cancer can be caused by simultaneous hypermethylation of other multiple genes as well as tumor suppressors (Lu et al., 2020, Majumdar et al., 2011). Epigenomic changes in specific tumors are discussed in other chapters of this book.

Recent advances in epigenetic editing have made it possible to precisely target cancer-promoting epigenetic factors. As a result, new cancer treatments are being developed that are more effective than traditional ones and have fewer side effects (Nepali & Liou, 2021). This chapter will highlight emerging technologies to regulate epigenetic alteration in cancer cells, which can be harnessed to develop novel cancer treatments and to understand cancer development. First, we introduce epigenetic alterations in cancer development and progression. Next, we briefly describe the methodology to modulate epigenomes in general, and finally, we discuss the advances and challenges of epigenome editing technologies in the application of cancer treatments.