Mutations (errors in the base sequence of DNA) can transform completely normal genes, which are responsible for cell growth, for example, into hyperactive, cancer-causing oncogenes. But even without mutations, genes can be over-activated by so-called epigenetic changes, thereby driving the growth of cancer cells. Epigenetic refers to mechanisms of gene regulation that are passed from cell to cell, but without changing the base sequence of the DNA. Epigenetic changes are reversible, i.e. they are basically reversible, which may make them suitable targets for therapies.
The research group of Dr. Dr. Sebastian T. Balbach focuses on epigenetic mechanisms in cancer of childhood and adolescence. In contrast to cancer cells of adult patients, cancer cells of young patients often have a very low mutation burden. These cancer cells are often “addicted” to the epigenetic hyper-activation of certain genes in order to be able to spread further. The research group “Epigenetic Mechanisms of Cancer (Stem) Cells” is working to elucidate the mechanism of dependence of cancer cells and cancer stem cells on specific epigenetic factors, to find new targets for targeted cancer therapies. During a two-year research stay in the group of Prof. Stuart Orkin at the Dana Farber/Boston Children’s Cancer and Blood Disorders Center of Harvard Medical School in Boston, Dr. Dr. Sebastian T. Balbach was able to identify potential new targets for the targeted therapy of pediatric tumor diseases. To this end, CRISPR-Cas9 technology screens were performed by knocking out individual genes in cancer cells in a highly targeted manner. The goal of these screenings was to determine which genes may be involved in the epigenetic regulation of cancer-causing oncogenes. The most promising candidate genes from these screenings are now under closer scrutiny.
For example, our research group was able to show that rhabdomyosarcoma cells will die if splicing, an important step in mRNA production in tumor cells, is disrupted because mRNAs essential for tumor cells can no longer be produced. The progress made in this work has now also convinced the German Research Foundation (DFG) to fund the project for two years with almost €240,000. The DFG project aims to clarify how compounds that block splicing work and whether in the future they could be used to treat rhabdomyosarcomas and other childhood and adolescent cancers.
