One of the fastest-moving fields in cancer research, epigenetics is the study of changes that influence how DNA does its job. Some of these alterations have been shown to cause cancer. Unlike most existing cancer drugs, which work by destroying cancer cells, therapies that target epigenetic changes have the potential to reprogram the diseased cells and set them on a path back toward normal growth and development.
Physician-scientists like myself and others at Memorial Sloan Kettering (MSK) are exploring a number of new drugs that interfere with certain epigenetic processes. If such drugs prove to be safe and effective in clinical trials, they may eventually offer a groundbreaking approach to cancer treatment.
As we look forward to the new possibilities that a new year brings, here are just a few reasons my colleagues and I are hopeful about the promise this growing field holds for our quest to reverse cancer.
1. New Insights Are Changing How We Treat Cancer
Epigenetic changes are a normal part of many biological processes -- for example, they allow immature cells in our bodies called stem cells to differentiate or develop into more-specialized types such as brain cells or skin cells. However, when changes take place in the proteins that control epigenetic processes, this can affect the expression of numerous genes that play a role in cancer initiation, development or progression.
The two epigenetic alterations we know the most about are methylation, a change on the DNA strand, and histone modification, a chemical reaction that regulates how tightly or loosely DNA wraps around a histone protein. Each of these two different mechanisms can influence which genes are expressed or translated into proteins, and activate genes that aren't usually turned on. They can also deactivate genes that are crucial to regulating proper cell growth and division by inhibiting their expression. These changes can lead to cancer and other diseases.
Ongoing research is helping us better understand these epigenetic changes and is providing insight into the broad differences between how DNA functions in cancer cells versus normal ones. The work is exciting because we are discovering that some of the enzymes that regulate these changes can be blocked with drugs.
2. Emerging Cancer Treatments Employ Search-And-Rescue Tactics
Traditional cancer treatments have aimed to eliminate cancer cells, by way of methods such as surgery, chemotherapy, radiation, and, more recently, through targeted therapies and immunotherapies. By contrast, epigenetic cancer treatment is more search-and-rescue than seek-and-destroy in its tactics, transforming cancer cells into normal cells instead of killing them. The method is showing early promise in treating certain kinds of leukemia and other blood cancers.
Leukemia occurs when immature cells are able to accumulate in the blood. These cells, which form in the bone marrow, contain mutations that prevent them from differentiating into specialized blood-cell types. If we can find drugs to block the enzymes that are preventing the cells from maturing in Leukemia patients, we may have a way to cure the disease.
This approach would be truly transformative -- both because it changes the way we look at cancer and because it literally transforms cancer cells.
3. Drugs That Target Epigenetic Changes Are Already Available
New drugs that work by targeting these epigenetic changes are already part of standard care for certain cancers. For example, azacitidine and decitabine both work by inhibiting the enzyme that allows certain DNA modifications to occur. These drugs are used for the treatment of a type of blood cancer called myelodyspastic syndrome.
Another class of enzymes that has been well studied is histone deacetylases (HDACs). These enzymes affect how tightly DNA strands in a cell's nucleus are wrapped around proteins called histones. If epigenetic changes cause them to be wrapped too tightly, genes in that region do not get expressed, or activated. The drug vorinostat -- an HDAC inhibitor largely developed at MSK -- was approved in 2006 for the treatment of cutaneous T cell lymphoma, an immune-cell cancer in the skin. Similar drugs in the clinical-trial pipeline include treatments for glioblastoma brain tumors and various types of adult and childhood leukemias.
4. We Are Seeing The Tip Of The Iceberg
Only in the past couple of years has this field of cancer epigenetics really taken off. It was sparked by the discovery that the ways histones and DNA are chemically modified are among the most prone to mutation. This caused enormous excitement among researchers because histone and DNA modifications can potentially be reversed with drugs.
We know of about 70 different ways histones can be modified. By better understanding how the processes work, we might be able to tap into untold opportunities to develop drugs that restore normal gene expression in cancer cells.
And the more we learn, the more we realize that this is only the tip of the iceberg.
There will never be one cure for cancer. There will be thousands -- thanks in large part to Memorial Sloan Kettering Cancer Center (MSK), the world’s oldest and largest private cancer center. With more than 130 years of experience delivering exceptional patient care, conducting innovative research, and spearheading outstanding educational programs, MSK believes science will continue to save lives every day and drive hope for the future.