Targeted Inhibition of Signaling Networks in Pediatric Glioblastoma Stem Cells
Most pediatric glioblastoma patients see an initial improvement after radiation and chemotherapy, but eventually succumb to their disease after the tumor evolves resistance. Treatment-resistant relapse usually arises from rare cell subpopulations (i.e. cancer stem cells), so we are focusing our efforts on identifying therapeutic approaches that specifically target the stem cells -- essentially, attacking the root of the cancer instead of pruning the branches. Cancer stem cells are rare, which makes them difficult to study because their specific properties are masked by the average properties of the rest of the tumor cells.
We have employed a new technological approach called "mass cytometry" that allows us to study the intracellular wiring of these cells in greater detail than was previously possible. From these studies, we hope to learn the genetic and environmental mechanisms that drive glioblastoma stem cell survival, and to identify drugs that specifically block these mechanisms in the cancer stem cells. Furthermore, by comparing glioblastoma stem cells from many different patients, we will learn whether the stem cells look and behave consistently across all patients, or whether there are a few distinct subclasses of glioma stem cells that should be treated differently. This information will be useful in designing personalized therapies that specifically kill the stem cells in each patient's tumor.
Ultimately, the goal of this research is to identify new potential drug targets and investigative therapies that achieve lasting remission by attacking the root of glioblastoma tumors -- the cancer stem cells.