Ovarian cancer affects approximately 22,000 women each year with disease frequently undetected until an advanced stage. Current therapy depends on using DNA damaging agents that take advantage of some ovarian cancers that cannot appropriately repair their DNA. While some patients will respond to therapy, a large portion will recur and die from their disease. There is an urgent and substantial need to improve therapies for these women. Our research focuses on the ability to determine which patients will respond to therapy by measuring poly(ADP-ribose) polymerase 1 (PARP-1) protein in patient with high-grade serous ovarian carcinoma (HGSOC). This protein indicates the ability for a cancer to repair DNA damage. High levels of DNA damage that are not easily repaired by the cancer result in high levels of PARP-1. It has been hypothesized that ovarian cancers with high levels of PARP-1 are more sensitive to DNA-damaging agents.

Through medical imaging (positron emission tomography [PET]) of PARP-1, we can measure PARP-1 levels in the tumor non-invasively and potentially identify patients who will benefit from DNA damaging anticancer therapies. This could prevent the unnecessary exposure of patients to these agents if there is no benefit and direct treatment to those most likely to benefit from powerful, though toxic, treatment. In this proposal, we will evaluate PARP-1 levels as a predictive tool to identify patients who will respond to therapy. Our first goal is to further validate our technology for measuring PARP-1 in a group of patients. Next, we will image patients for PARP-1 before they receive therapy and then follow the patients throughout the course of their disease to evaluate whether PARP-1 levels can predict response to therapy. Lastly, we will image PARP-1 before and after therapy to measure changes in PARP-1 levels to determine whether changes in the levels of the PARP-1 protein are early signs of response.

By validating our technology for the medical imaging of PARP-1, we offer a non-invasive way to measure DNA damage in ovarian cancers and predict response to therapy. Through the completion of the outlined proposal, we will be able to determine the clinical significance of PARP-1 and expand to larger clinical trials for further evaluation with the potential to greatly improve the treatment for women with ovarian cancer.