Epigenetic therapy is a medical treatment that influences how genes are expressed without altering the actual DNA code. This approach targets the intricate systems cells use to control which genes are active or inactive. By manipulating these control mechanisms, epigenetic therapies can address the underlying drivers of various diseases.
Understanding Epigenetic Modifications
The human body contains a vast set of genetic instructions known as the genome. Epigenetics refers to the chemical modifications that act upon this genome to regulate gene activity. This layer of control dictates which genes are turned on or off, allowing cells with the same DNA to differentiate into various types, such as muscle cells or skin cells.
A useful way to conceptualize this is to think of DNA as a comprehensive cookbook, where genes are the individual recipes. Epigenetic marks are like sticky notes and bookmarks that a chef uses to indicate which recipes to cook and which to ignore. These notes don’t rewrite the recipes but guide their use, and this system can be influenced by environmental factors like diet.
Two primary types of epigenetic modifications are DNA methylation and histone modification. DNA methylation involves attaching small chemical tags, called methyl groups, directly onto the DNA. When a gene is methylated, it is turned off, preventing the cell from reading its instructions and producing the corresponding protein.
Histone modification offers another way to control gene access. Histones are proteins that act like spools, around which DNA is tightly wound to fit inside the cell’s nucleus. Chemical groups can be added or removed from these spools, which alters how tightly the DNA is wound. If the DNA is wound tightly, genes are hidden and turned off, while looser DNA makes genes accessible and turns them on.
How Epigenetic Therapies Work
When errors occur in these epigenetic processes, they can lead to the development of diseases. Conditions such as cancer are often associated with aberrant epigenetic patterns where genes are incorrectly activated or silenced, disrupting the normal balance of cellular function.
In many forms of cancer, for instance, protective genes that stop tumor growth—known as tumor suppressor genes—can be mistakenly silenced by epigenetic marks. At the same time, genes that promote cell growth, called oncogenes, might be inappropriately activated. This faulty regulation allows cancer cells to multiply without normal checks.
The goal of epigenetic therapy is to correct these errors. These treatments are designed to interact with the cellular machinery responsible for placing or removing epigenetic marks. By doing so, they can erase the incorrect silencing marks on tumor suppressor genes, allowing them to be turned back on and resume their protective functions.
Conversely, these therapies can also help re-establish silencing marks on oncogenes that have been wrongly activated. This approach aims to restore the normal pattern of gene expression, compelling cancer cells to behave more like healthy cells. The strategy is to rewrite the faulty instructions layered on top of the DNA.
Medical Applications of Epigenetic Therapy
The primary field where epigenetic therapies are used is oncology, particularly in the treatment of blood-based cancers. These therapies provide an option for patients with specific malignancies that have been difficult to treat. The U.S. Food and Drug Administration (FDA) has approved several epigenetic drugs, establishing them as part of standard cancer care.
Among the most prominent applications is the treatment of myelodysplastic syndromes (MDS), a group of cancers where immature blood cells in the bone marrow do not mature properly. Epigenetic drugs can improve blood counts for these patients. Certain types of leukemia, like acute myeloid leukemia (AML), and lymphomas, such as cutaneous T-cell lymphoma (CTCL), are also treated with these agents.
While the success in blood cancers is well-established, applying epigenetic therapies to solid tumors has been more challenging, though it remains an active area of investigation. Beyond cancer, research is expanding to explore their use for other conditions. Scientists are studying their application in neurological disorders, including Alzheimer’s disease, and in autoimmune diseases.
Classes of Epigenetic Drugs
The drugs used in epigenetic therapy fall into two major categories: DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors. Each class works by targeting the specific enzymes responsible for adding or removing the chemical tags that control gene expression.
DNMT inhibitors are designed to counteract DNA methylation, the process that often silences tumor suppressor genes in cancer. These drugs work by blocking the action of DNA methyltransferase enzymes, which add methyl groups to DNA. This blockage results in the reactivation of previously silenced protective genes. Azacitidine is an example of an FDA-approved DNMT inhibitor used to treat myelodysplastic syndromes.
HDAC inhibitors work on histone modification. In many cancers, histone deacetylase (HDAC) enzymes are overactive, removing acetyl groups from histones, which causes the DNA to wind more tightly and silence genes. HDAC inhibitors block these enzymes, which allows the chromatin structure to relax and unwind. This makes genes accessible again, reactivating their expression. Vorinostat is an HDAC inhibitor approved for treating cutaneous T-cell lymphoma.