Presenter(s): Corinne Togiai
Faculty Mentor(s): Bill Chang
Oral Session 3 M
Acute Lymphoblastic Leukemia (ALL) is a common cause for disease-related mortality in children and adolescents. As we have made great strides in curing ALL we have identified subsets of diseases that continue to have a poor prognosis. To develop novel targeted therapies in hopes to advance the treatment of these diseases, our lab initiated the use of rapid, state-of-the-art genetic and functional assays to identify aberrant activated pathways from primary patient leukemic samples. Results through collaborative research with the Knight Cancer Institute Leukemia Research Group, have identified significant hypersensitivity to different cellular pathway inhibition. Our current proposal builds on these findings. We have identified a unique hypersensitivity of certain subsets of leukemic cells to inhibition of the Aurora class of cell cycle kinases. Aurora kinases are members of serine/threonine kinases that play pivotal roles for the cell to faithfully undergo mitosis. Studies have shown that certain cancers are heavily dependent on the activity of these kinases beyond mitosis and that these kinases can be targeted by specific small molecule drugs. Our preliminary data is the first to identify subsets of ALL that are hypersensitive to aurora kinase inhibition. What remains unknown is the mechanism of hypersensitivity in subsets of ALL as well as in vivo validation.
Other future directions in parallel aim towards determining the mechanism of hypersensitivity to Aurora kinase inhibitors in subsets of ALL, and developing in vivo models testing single agent and combination therapy specifically targeting these pathways.