Epigenetic drugs and what could they be used to treat - Sarah Heerboth, Karolina Lapinska, Nicole Snyder, Meghan Leary, Sarah Rollinson and Sibaji Sarkar.

The whole human body is like a complex computer network from head to toe. However, the complexity of the human body is greater, because unlike electronic devices, the circuits vary or fluctuate according to inputs, signals, and cellular and genetic changes. Interestingly, a lot of stimulators which make these changes come from the environment. In the cellular context, the environment could be the surrounding tissues and the chemicals they secrete. Contrary to an electrical system, the human biological circuitry can be reversibly changed by shutting down one pathway and turning on another. These changes can be irreversible if they are caused by mutations and alterations in genes and chromosomes, and can be reversible if they are caused by epigenetic changes.

Proteins carry out the majority of the cells work. Essentially, a defective protein in a vital pathway of cell survival, cell development, or function could adversely affect the entire cell. When genetic mutations cause these changes, they can be irreversible. Alternatively, epigenetic changes do not change the genetic code and can be reversible. Proteins are produced from RNA that carries a coded message from the gene made of DNA. A mutation in a gene produces altered RNA, and thus, can produce a defective protein. In epigenetic changes, the modification of the segment of DNA often results in increased or decreased RNA production, because the modification often affects the histones or regions of the gene that control the amount of RNA production.

Many of these changes either come from signals from the environment or from the cells surrounding a particular tissue. During the development from embryo to a human being, we need to develop versatile tissues and organs from the same original cell, which requires turning on and shutting off many pathways without losing the gene pool we inherited. These types of changes are not uncommon in a healthy person. Epigenetics plays a huge role in this process.

In certain conditions, however, these changes can be harmful. Recent research has shown that alterations of protein expression due to the increase or decrease of RNA formation by epigenetic mechanisms may alter the balance around tissues that can lead to many diverse diseases and disorders.

Examples of these types of diseases include neurological, cardiovascular, and metabolic problems, as well as cancer. Theoretically, reversal of these changes could fix the problem or improve the condition. Epigenetic drugs are under development and recent studies show that they are capable of changing the imbalance for cure or management of disorders and diseases.

In cancer, the epigenetics events are well studied. Many genes which keep uncontrolled cell growth under check are silenced (do not produce proteins) by epigenetic mechanism. We recently proposed that epigenetic events initiate cancer progenitor cell formation. These progenitor cells are usually not killed by normal cancer therapeutic agents, and hence, cancer relapses. Epigenetic changes are also involved in cancer dug resistance. Recent studies suggest that combination therapy including epigenetics drugs possibly will reduce cancer relapse and will make resistant cancer cells susceptible. Further research is in progress to address these issues.

This group are the authors of the recently published paper Use of Epigenetic Drugs in Disease: An Overview, available for download now in Genetics & Epigenetics

 

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