Epigenetics refers to the examination of biological mechanisms related to heritable (proportional) changes in phenotype (appearance) or the genetic expression of a cell that is unrelated to the normal or anomalous sequencing of DNA. Once a relatively obscure field of scientific investigation, epigenetics is fast approaching the forefront of cancer research as more and more geneticists seek new clues about cellular mechanisms and behaviors that DNA-based studies have failed to provide.
While the field of epigenetics has existed for decades, it had remained a little known and even less pursued area of cancer research until the 1990s, at which time excitement over the Human Genome Project (HGP) had reached a fever pitch. From 1989 to 2003, medical researchers had labored tirelessly to create a detailed genetic map of the approximately 20,000 separate and distinct genes that serve as the blueprint for the human body. It was hoped that once each individual gene had been isolated, clearly identified, and studied, the mystery of uncontrolled cancer cell growth would be revealed.
During the height of cancer research optimism related to the HGP, biological mechanisms unrelated to genetic coding had been considered to be of little or secondary importance to the study of neoplastic disease. Scientists were convinced that the HGP would provide them with an abundance of genetic clues that would lead them straight to the heart of a cure for all types of cancer. When it was discovered that healthy cells and cancer cells alike, from the standpoint of DNA sequencing, were substantially undifferentiated, researchers began to look outside the genetic code in an attempt to understand why cells with identical DNA sequencing could take such dramatically different routes of development-normal cellular mitosis (division), versus uncontrolled cancer cell replication. If the answer wasn’t in the DNA, where else could researchers turn to unlock the stubborn and unyielding mysteries of cancer?
Looking at cancer in a New Way
While the HGP still provides us with an invaluable blueprint of the human body, the epigenome can be compared to a building contractor who oversees a grand plan to ensure that a building is properly constructed. Scientists are now taking a closer look at how a genome is tagged and assembled within a cell’s nucleus. As a result of such investigations, scientists seek to discover the epigenetic cues a cell is given in order to maintain normal biological behaviors throughout its lifetime.
Epigenetics can be compared to a light switch because it has the ability to turn cells on and off, which is why a lung cell will look and behave differently than cells from a kidney or a spleen. Epigenetics holds the promise of providing cancer researchers with valuable new clues as to how and why healthy cells lose their ability to regulate growth, and initial skepticism about such research has been replaced with widespread optimism and significant increases in funding. It was recently announced that the federal government’s National Institutes of Health will provide epigenetics researchers with $190 million in funding over the next five years-in the near future, similar appropriations from other cancer research funding programs are expected to follow.
Epigenetic Changes in Cell Biology
Cancer and other health researchers have now identified two ways in which epigenetic changes occur-the first is known as methylation, which refers to a biological process that includes the binding of methyl groups (chemical clusters) to a cell. These methyl groups will usually instruct encoded proteins to limit their own production. Methylation is a natural biological mechanism, but, if too few or too many methyl groups bind to a cell (for example), tumor suppressor genes can become damaged or inactive. Many cancer researchers believe that the growth of all malignant tumors will eventually be shown to have been associated with epigenetically deactivated tumor suppressor genes.
The second way epigenetics alters cellular behaviors has to do with the way genes are bundled together. In order to insert long lengths of genetic material into the microscopic nucleus of a cell, proteins known as histones facilitate the compaction of genetic codes into tightly wound chromosomal structures that are not wholly unlike a ball of twine. Problems can arise because of the way this metaphorical twine is coiled around a cell.
Genetic codes that are most needed by a cellular structure will be wrapped more loosely, thus allowing easier access to the information stored there. If this twine is wrapped too tightly, a cell may not be able to decipher the critical cell function information it needs to achieve non-neoplastic mitosis. Conversely, if these genetic encoded strands are wrapped too loosely, a cell may extract harmful information that would have otherwise been unavailable-malignant neoplasm being the result.
Armed with knowledge about epigenetics, cancer researchers have been able to develop new cancer-fighting drugs such as Dacogen (decitabine) Vidaza (azacitidine), and Zolinza (vorinostat), all of which are demethylating agents that have proven to be effective treatments for a variety of cancers. As researchers learn more about epigenitics, new antineoplastic analogues will undoubtedly be developed to attack what may be cancer‘s weakest link.