Project 172024

Radiation therapy (RT) plays a significant role in cancer treatment, and has until recently been thought to be curative by mainly killing tumor cells directly by damaging their genetic material (DNA). However, recent findings indicate that the tumor vascularity is also a major determinant of radiation response. Currently, advanced volumetric imaging techniques are employed to guide the delivery of RT in patients based on changes in the tumor's size or volume (i.e., geometric/anatomical metrics) over the course of treatment. Treatments are largely empirically derived and ignore variations in the radiosusceptibility of the vascular component. What is critically needed is a more biologically-informed way to optimize conventional radiation treatment. Therefore, the long-term goal of this project is to optimize radiation treatment based on the biological (vascular) responses monitored 'on-line' during treatment. The immediate goals of this first 3-year phase are a) to better understand the dynamic processes involved in tumor cell death, vascular damage and tumor microenvironment signaling during response to radiation therapy and b) to develop and validate optical 'smart' probes of vascular/cellular responses that could ultimately be used for minimally-invasive and real-time monitoring of these molecular signals to enable adaptively optimized treatment in individual patients. We will exploit advanced optical imaging technologies combined with emerging molecularly-sensitive 'smart' optical agents to probe the temporal dynamics of tumor cell death and vascular damage caused by radiation therapy at cellular and molecular levels. We believe that this will lay the groundwork for future 'breakthrough' strategies of this treatment modality, thus profoundly impacting the effectiveness of clinical radiation therapy.