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.
Part of the book: Advances in the Molecular Understanding of Colorectal Cancer
The proinflammatory transcription factor nuclear factor-κB (NF-κB) has emerged as a central player in inflammatory responses and tumor development since its discovery three decades ago. In general, aberrant NF-κB activity plays a critical role in tumorigenesis and acquired resistance to chemotherapy. This aberrant NF-κB activity frequently involves several post-translational modifications of NF-κB, including phosphorylation. In this chapter, we will specifically cover the phosphorylation sites reported on the p65 subunit of NF-κB and their relationship to cancer. Importantly, phosphorylation is catalyzed by different kinases using adenosine triphosphate (ATP) as the phosphorus donor. These kinases are frequently hyperactive in cancers and thus may serve as potential therapeutic targets to treat different cancers.
Part of the book: Adenosine Triphosphate in Health and Disease
Drug discovery is an exciting yet highly costly endeavor. In the United States, developing a new prescription medicine that gains marketing approval takes near a decade and costs drugmakers for near 3 billion. More challengingly, the success rate of a compound entering phase I trials is just slightly under 10%. Because of these mounting hurdles, repurposing market approved drugs to new clinical indications has been a new trend on the rise. Another merit to this approach is the already confirmed toxicity profiles of the drugs and their possession of drug-like features. Thus, repurposed drugs can reach the market approved stage in a much faster, cheaper, and more efficient way. Notably, epigenetic enzymes play a critical role in the etiology and progression of different diseases. Researchers are now assessing the possibilities of using market approved drugs to target epigenetic enzymes as a novel strategy to curtail disease progression. Thus, in this book chapter, we will provide an outlook on repurposing market drugs to target epigenetic enzymes in various diseases. Consequently, this book chapter will not only provide the readers with current knowledge in this specific field, but also will shed light on the pathway forward for repurposing market drugs to target epigenetic enzymes in human diseases.
Part of the book: Drug Repurposing