Correlative biology that supports clinical translation and guides future studies: A major focus of our translational studies is understanding the relationships between drug exposure and target suppression both in vitro and in vivo.  In addition, we have worked to develop methods to quantitate target suppression in tissue. 

A number of years ago, we recognized the need for a pharmacodynamic marker of EWS-FLI1 suppression. We found that 18F-FLT PET reflects EWS-FLI1 activity because the fusion protein drives expression of the proteins responsible for tracer activity. It is notable that this effect is not related to perturbation of the cell cycle.

Future directions, goals and current projects: We are now collaborating with investigators at Penn and the NCI to evaluate this tracer in patients in the clinic. In addition, we are using the tracer in our preclinical studies to examine the contribution of tumor architecture to EWS-FLI1 suppression. Finally, we have expanded our translational efforts trying to better understand mechanisms of drug sensitivity and resistance using patient tissue collected on our study.