Nanoparticle and biomaterial drug delivery systems have become powerful tools in cancer treatment because they enable tumor sites to be targeted more directly, thus decreasing toxicity and increasing efficacy. This project will combine a nanoformulation of Talazoparib (TLZ), a PARP inhibitor, with ADU-S100, a STING agonist, for ovarian cancer treatment. Poly(ADP-ribose) Polymerase (PARP) inhibitors are a class of cancer drugs used to treat BRCA-deficient ovarian cancer by interfering with DNA repair pathways, leading to further cell damage and ultimately cell death. They are traditionally administered orally, which requires a high drug load, resulting in adverse side effects, particularly in more potent types such as TLZ. Previously, a sustained delivery implant consisting of poly (lactic-co-glycolic) acid (PLGA) loaded with TLZ was shown to improve efficacy and lower toxicity in mouse models of ovarian cancer, however the response was not durable, and resistance develops. STING agonism has been demonstrated as an approach to overcome PARP inhibitor resistance in breast cancer models, but its translation efficacy in ovarian cancer has yet to be investigated. Our objective is to combine PARP inhibitor formulations with STING agonists to test the long-term durable response in a metastatic, patient-mimicking ovarian cancer model. A biodegradable sustained delivery implant of TLZ will be used in combination with ADU-S100 to investigate the synergistic therapeutic effects of the treatments together. In vitro studies will be carried out to assess DNA damage and treatment efficacy, and in vivo proof-of-concept studies using mouse models injected with BRCA-deficient ovarian tumors will track tumor growth and survival following treatment.

CaNCURE Research Presentation: https://youtu.be/sYWmIqLXw44