Project: Epigenetic Mechanisms of Resistance in T-cell Acute Lymphoblastic Leukemia
Acute t-cell lymphoblastic leukemia (T-ALL) makes up about 15-20% of leukemia diagnoses in children and adolescents. T-ALL has high rates of relapse and is often resistant to treatment. Cancer that is resistant to treatment is called refractory disease. When a child with T-ALL relapses or has toxicity problems and cannot tolerate standard chemotherapy treatments, there are almost no alternative treatment options.
Dr. Birgit Knoechel at Dana-Farber Cancer Institute is trying to change the odds for children and young adults with T-ALL. Her research examines new epigenetic targets for this disease and uses these findings to discover new treatments that might be used for those children without other treatment options.
Epigenetics is the study of information in a cell that is not encoded in the DNA but can be maintained and passed on through cell division. In recent years, researchers have learned much more about epigenetics. In cancer cells, epigenetic marks communicate a kind of cellular “memory.” Although it is difficult to target cancer genes, it is possible to target epigenetic markers and by doing so, researchers believe they can create innovative and less toxic treatments for cancer. These targeted treatments present a much-needed alternative for children in whom standard therapy has failed. However, in order to ensure that the targets will be effective, researchers first need to prove that these different types of cancer have these unique epigenetic markers and that they are vulnerable to epigenetic treatments.
Dr. Knoechel has received a grant from CureSearch to explore the role of EZH2, an enzyme that is involved in a number of cancers. When this enzyme is over-expressed, it silences tumor suppressor genes and allows cancer to grow and spread. Inhibiting EZH2 may also prevent T-ALL from spreading. Since a number of FDA-approved compounds already exist to target EZH2, this research could be translated quickly to clinical trial. We look forward to sharing updates on Dr. Knoechel’s research over the next 3 years.