11100 Euclid Ave.
Cleveland, OH 44106
07/28/2011

During the four years preceding this application, the Division of Pediatric Hematology-Oncology at Rainbow Babies & Children’s Hospital has successfully recruited several new faculty members, who together have established a new research initiative focused on the biology of Cdk5. To date, this research team has identified a novel role for this kinase in T cell biology and the relevance of this kinase as a therapeutic target in several childhood cancers, including leukemia. This research team currently seeks to translate this knowledge into a clinical application, starting with a ‘first in children’ Phase I trial with a novel inhibitor of Cdk5.

To do so, we are in the final stages of completing testing of this inhibitor in a series of in vivo preclinical models of pediatric cancers, and will refine a set of biomarkers that will be utilized as an important panel to assess efficacy of novel small molecule inhibitors in disruption of the activity / function of Cdk5 in vivo. With the current funds from Hyundai, Dr. Egler will facilitate the critical next step by developing clinical research infrastructure at Rainbow and by soliciting participation and establishing needed liaisons with collaborating institutions. Investigators at these institutions may contribute through patient enrollment, protocol development and specimen biomarker evaluation. Thus, a major endpoint for this effort will be successful development and implementation of a Phase I clinical trial, through which we will explore the safety and kinetics of Cdk5 inhibition in pediatric patients. Thus, this effort will create new opportunities for clinical trials participation, and offer hope for patients for whom our currently best available therapies have not been successful.