Unusual changes to your DNA activity can lead to cancer. Researchers are using this knowledge to create treatments that can undo these alterations.
What Is Epigenetics?
While cells have specific jobs for various parts of your body, the DNA inside them is almost the same. What makes them different is how and when they turn on or off sets of genes.
Cells can control and activate or deactivate the genes they need through epigenetic changes. These are small alterations to the DNA and proteins within the cell’s chromosomes. These changes temporarily adjust how cells use DNA information without modifying your DNA sequence. Your body needs epigenetics so the right genes are on in the right cells.
Changes That Cause Cancer
Cancer can develop when epigenetic changes go wrong. They can affect the two main groups of genes with cancer connections -- oncogenes and tumor suppressor genes. Oncogenes can become too active, and tumor suppressor genes may change or go away.
Your cells aren’t the only things that can trigger epigenetic changes, which are also known as epimutations. Things like smoking, not exercising enough, drugs, your diet, and environmental chemicals or radiation can cause abnormal adjustments to the activity of your genes or DNA outside of genes that can result in cancer.
Your parents can also pass down epigenetic information. Doctors call this “transgenerational inheritance.”
What Epigenetics Means for Cancer Treatment
As scientists learn more about epigenetic changes in cancer cells, they’re trying to create treatments that reverse them. One of the best parts of these therapies is that they don’t kill cells, unlike chemotherapy and radiation. They simply adjust how cells work by attacking (or inhibiting) certain enzymes (proteins).
Scientists are mostly studying drugs called DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors. These drugs show promise for some cancers, but the ones available now don’t seem to work against solid tumors.
DNA Methyltransferase (DNMT) Inhibitors
DNA methylation determines how active a gene is. Genes are on when there is little methylation. Genes are off when there is a lot of methylation. During cancer, tumor suppressor genes usually have lots of methylation. The goal of DNA methyltransferase (DNMT) inhibitors is to make genes, including tumor suppressor genes, active again.
There are two kinds available:
- Azacitidine (Vidaza)
- Decitabine (Dacogen)
Doctors use them to treat conditions like myelodysplastic syndrome and acute myeloid leukemia. These drugs stop the enzymes that cause methylation from turning off other parts of DNA. Unfortunately, these treatments also break down very quickly in your body, often in less than an hour. They can make your immune system less effective and damage DNA as well.
Zebularine is an exciting newer drug that researchers are exploring because it is safer, more stable, and effective. It works similarly to the DNMT inhibitors available now and makes genes active again in cancer cells.
Histone Deacetylase (HDAC) Inhibitors
Histones are a type of protein that organizes DNA to fit into chromosomes. Epigenetic factors that change histones make the DNA readable or unreadable. Histone acetylation is one way to make the DNA readable, which raises gene activity. Histone deacetylation makes the gene unreadable and silences it. A lot of histone deacetylation activity happens in different kinds of cancer cells. Scientists believe this is linked to tumor suppressor and DNA repair genes being silent.
Histone deacetylase (HDAC) inhibitors should reduce histone deacetylation, which helps tumor suppressors be more active. Doctors currently use these inhibitors:
- Belinostat (Beleodaq)
- Panobinostat (Farydak)
- Romidepsin (Istodax)
- Vorinostat (Zolinza)
Though these treatments work for blood cancers like leukemia, myeloma, and lymphoma, they have drawbacks. They damage bone marrow and may lower blood cell counts. They can also cause side effects like diarrhea and fatigue. The fact that these drugs go after every HDAC, not just the ones that affect cancer cells, is probably one cause of these side effects.
Epigenetics and Other Cancer Treatments
Sometimes doctors must use different kinds of cancer treatments at once. Epigenetic drugs seem to work well with radiation and chemotherapy. The drugs may make cancer cells more sensitive to these therapies, making them work better and more likely to prevent cancer from coming back.
Your doctor can also use more than one epigenetic drug at a time. The doses of the drugs you get are often much lower, which can limit side effects. But combining them can make them more powerful.