Rui Zhang
LSU, College of Science, Department of Physics and Astronomy
Project Title
Pre-clinical investigation of precision immunoradiotherapy for breast cancer
Funding Period
Pilot (June 7, 2022 - February 28, 2023)
Biosketch
The goal of the proposed research is to search for optimal and personalized immunoradiotherapy protocols for breast cancer patients through pre-clinical studies. Upon completion, we will have tested various combinations of dosages and timing, evaluated the potential predictive biomarkers, and generated rigorous pre-clinical evidence for breast cancer treatment and future large-scale investigations. I am particularly well suited for my role in this project because I have the expertise and motivation necessary to carry out the proposed work successfully. I have a solid background in medical physics and cancer research, and I am board certified in Therapeutic Physics by the American Board of Radiology. So far, I am the first author or co-author of 48 peer reviewed papers and many more under review or in preparation. At Louisiana State University, the start-up funds and university-funded grants helped me establish my own research lab, build research infrastructure and publish more peer-reviewed papers. I also benefited from the NIH K22 grant, which provides protected time for me to develop independent research directions. Besides those, I also learned how to manage a big research project, maintain a research group, and collaborate with other researchers. For this project, I have teamed up with Drs. Huang and Guo as co-investigators to provide expertise in immunotherapy, pre-clinical experiments, immune response assessment, outcome evaluation, statistical modeling, trial design, uncertainty and statistical analyses. In summary, I have demonstrated both research skills and productivity to be the principal investigator. I have the right research team and an excellent environment to accomplish the proposed project.
Abstract
Breast cancer is a global health problem, and there are about 3.8 million breast cancer survivors in the US. Recently, immunotherapy (IT) has revolutionized breast cancer management with outcomes that have not been previously achieved. Nonetheless, IT alone presently only benefits a minority of patients, and additional interventions are needed to overcome the immune resistance for most patients. The emerging knowledge of radiotherapy (RT)-induced systemic immune response has increased the enthusiasm for combinatorial immunoradiotherapy (IRT) for breast cancer patients. However, our understanding of the influence of RT characteristics on immune stimulatory and suppressive effects is largely incomplete. IRT follows the traditional sole RT and IT protocols, and the optimal combination is undetermined. Furthermore, patients’ responses to treatment remain heterogeneous, but precision IRT protocols for specific patients are completely lacking, in part, due to the lack of reliable biomarkers. There is an urgent need to optimize IRT protocol, maximize the synergy of radiation and immune response, and take into account patient’s personal features. Investigation of these issues by clinical trials is impracticable due to a multitude of variables involved, high risks and high expenses. The goal of this project is to search for optimal IRT protocols for breast cancer through pre-clinical studies. Upon completion, we will have tested various combinations of dosages and timing, evaluated the potential predictive biomarkers, and generated rigorous pre-clinical evidence for future large-scale investigations.