Epigenetic mechanisms of hepatocellular carcinoma progression: Potential therapeutic opportunities

Among all the primary liver cancers, hepatocellular carcinoma (HCC) takes up the major stake, representing 85%-90%, and is refractory to nearly all currently available anticancer therapies. HCC is the fifth most common cancer in the world, leading to nearly 600, 000 deaths worldwide annually. A healthier approach is needed to understand HCC molecular pathogenesis, which becomes crucial for the prognosis, earlier diagnosis, and development of effective treatments. The multistep liver carcinogenesis process results from the build-up of innumerable genetic and epigenetic alterations. Mutations in essential genes as well as alterations in DNA methylation, histone post-translational modifications (PTMs), and noncoding RNA expressions substantially contribute to HCC progression by disrupting gene regulation networks. In the majority of HCCs, multiple genes show structural changes essentially affecting several regulatory pathways. Because of such genomic complexity in HCCs, and the changes in the genomic sequences are irreversible, active molecular genetic therapy presents a major task. In the landscape of current biomedical research, epigenetics is one of the escalating and most hopeful fields. From an operational standpoint, the initial single gene candidate approaches which were successful are in need to be complemented by the current comprehensive epigenomic approaches. In this book chapter, I will summarize the current knowledge we have on epigenetic alterations during HCC progression and pathogenesis. I will also try to highlight the principal challenges as well as the associated therapeutic opportunities to overcome this health emergency.