Inhibition of Cathepsins to Treat Neuroblastoma
Inhibition of Cathepsins to Treat Neuroblastoma Neuroblastoma is a common pediatric cancer that is characterized by abnormal continuous proliferation of neural crest cells late in development. In most infants, this abnormal proliferation spontaneously regresses and clinical management is restricted to surgical removal of large tumors and observation of disease regression. This is particularly striking for stage 4S where even multiple secondary tumors regress. By contrast, tumors that persist in children beyond 2 years of age are particularly refractive to treatment and prognosis for these children remains poor. We have discovered that treatment of neuroblastoma cells with a compound that specifically inhibits two proteases causes cell death. Other rapidly growing cells are not affected leading us to propose that inhibition of these proteases may provide a new way to treat neuroblastoma that is not harmful to other cells in growing children. A unique aspect of this study is that we are aiming to promote molecular pathways that occur during normal neural crest cell differentiation rather than targeting abnormal features of individual tumors. In this proposal we plan to determine how this compound selectively kills neuroblastoma cells so that we can design more effective treatments. If this study is successful we predict that it will emerge as a novel therapeutic intervention for neuroblastoma.