Chemistry Proposal Defense — Emily Savoy

About the event

Title: Module Smart Molecules for PSMA-Targeted Chemotherapy

Abstract: Prostate cancer is a dynamic and heterogeneous disease, necessitating a diverse arsenal of targeted chemotherapeutic agents for treatment. The cell-surface enzyme prostate-specific membrane antigen (PSMA) is a hallmark biomarker for targeted therapy and imaging of prostate cancer. While considerable efforts and significant advances have been made in the development of PSMA-targeted chemotherapeutic agents such as antibody-drug conjugates (ADCs) or small-molecule drug-conjugates (SMDCs), limitations and challenges remain. The long-term goal is to develop a scaffold that can be broadly applicable in the field of PSMA-targeted SMDCs, providing selective uptake in target tissues, sparing healthy tissues, and circulating sufficiently for optimal accumulation of a therapeutic dose in tumor cells. A targeted small-molecule chemotherapeutic for prostate cancer can be developed by harnessing the affinity and cell-penetrating properties of irreversible PSMA inhibitors coupled to a universal pH-triggered cleavable linker system. Preliminary data suggests that our first PSMA-targeted SMDC is efficacious in a mouse model and spares non-target tissues, such as kidneys, salivary glands, and lacrimal glands. With these successes, we are positioned to develop a panel of effective PSMA-targeted SMDCs through a modular assembly approach.