V Scholar Plus Award- extended funding for exceptional V Scholars
Gene regulation is vital for our health and abnormal regulations lead to many diseases, including cancer. There are two mechanisms that control genes: Genetic info and epigenetic. Genetic alterations are stable and we cannot target them. However, epigenetic is dynamic as it changes over time. Epigenetic can control gene expression in tissues. It is the loss of this control that causes cancer. In cancer, only select genes are abnormal while the rest are normal. We need to target only abnormal genes. Current therapy is based on chemicals that target all of the genes in the cell. Thus they have side effects. This proposal develops a novel tool that can target a specific gene. Thus, it can correct an aberrant gene only. The tool also has strong therapeutic potential. This will be very valuable for basic research.
“Precision medicine” aims to develop better treatments by understanding the molecular causes of disease. This is essential in cancer because each type (breast, brain, or blood cancer, for example) represents dozens of different kinds of cancer at the molecular level. And each of these different molecular sub-types requires different treatments.
Based on research of the past twenty years, we understand a great deal about what drives cancers. Many drugs have been devised that specifically target these causes – molecular “smart bombs.” However, the cancer cells rapidly adapt and find escape routes. Drugs that seem to work ultimately fail. We get many hopeful responses but few cures.
Our research seeks to identify and block these escape routes. We look at the molecular changes inside cancer cells after drugs are applied, and we then use other drugs to “slam the door” so the cancer cannot escape treatment. Our approach is already proving successful: We are testing one of these combinations in people to treat Mantle Cell Lymphoma. We propose to look at similar cancers that might benefit from this approach. We also want to better understand ways that cancer cells might escape from our combination treatments. Our goal is to improve responses to therapy and turn temporary responses into real cures.
