Epitranscriptomic mechanisms of therapy resistance in high-risk neuroblastoma

Dr. Liron Grossmann, M.D. – The Sheba Fund for Health Service and Research, Israel

Neuroblastoma is a fatal childhood cancer with approximately 50% chance of recurrence despite multiple lines of aggressive therapies. Therefore, new therapies are urgently required to fight this devastating cancer. Our group has recently identified and characterized the malignant cells that survive chemotherapy in neuroblastoma patients. We found that neuroblastoma cancer cells may alter the levels of proteins which allow them to resist chemotherpay. They do so by chemically changing certain RNA molecules, which are derivatives of the DNA. The altered RNA molecules lead to changes of the these important proteins, which result in drug resistance. In this project, we ask: "how does chemotherapy change the chemical structure of RNA molecules in a way that allow neuroblastoma cells to survive instead of dying?". Together with our collaborators, who are world experts in RNA chemical modifications, we will use advanced technologies to study the differences in RNA chemistry before and after chemotherapy and identify the proteins that allow neuroblastoma cells to escape chemotherapy. If successful, our results may lead to the discovery of new therapies that prevent the RNA molecules from being chemically changed and kill the remaining neuroblastoma cells. Thus, our project has the potential of changing the way we currently treat children with neuroblastoma and improve their chances of surviving.