HDAC inhibition in cancer

Epigenetics is an important field of science that is focused on understanding the changes in gene expressions that are enforced without any genotype (DNA sequence) modifications. Epigenetic alterations affect the physiological and pathological status of the body by influencing molecular and cellular functions. Though epigenetic changes are a natural occurrence, they can be regulated by several factors, including age, environment, lifestyle, and cellular homeostasis. Epigenetic modifications can be manifested as developmental changes such as differentiation of cells or changes in organ functions that can lead to more detrimental effects and result in diseases like cancer. Research around the world is continuously uncovering the role of epigenetics in a variety of human disorders and fatal diseases. Because of the continually emerging research findings, which can be attributed partly to the use of modern research methodologies, understanding and appreciation for the complexity and plasticity of epigenetic alterations have dramatically increased in the last few years. Integration of the next-generation sequencing (NGS) approach with well-established techniques such as chromatin immunoprecipitation (ChIP-Seq) has presented scientists with a more efficient view of the epigenome and its transformation. Also, newer technologies have enabled the achievement of comprehensive maps of nucleosome positioning, chromatin conformation, transcription factor binding, localization of DNA, and histone modifications in various conditions. As a result of these advancements, now scientists have a greater knowledge of the facts, such as when the genome is transcribed and when the noncoding RNA may play a significant role in gene regulation. Recent advances in the field of epigenetics have shown that human diseases including cancers harbor epigenetic abnormalities, in addition to numerous genetic alterations, that determine the disease progression and treatment outcomes. The epigenetic alterations can interact with genetic mutations at all stages of cancer development, and progression and therefore, become biomarkers for detection and targets for treatment. In this chapter, we take a comprehensive look at the current understanding of epigenetic alterations and related mechanisms that can be targeted by available therapeutic agents.