Dr. Gail Matters’ research focuses on novel ways to diagnose and treat pancreatic cancer. In collaboration with Dr. James Adair’s lab at University Park, she has demonstrated effective encapsulation of phosphorylated analogs of the chemotherapy drugs 5-FU and gemcitabine into calcium-phosphosilicate nanoparticles (CPSNPs). Her research group also has identified DNA aptamers, small oligonucleotides, which bind to receptors on the surface of cancer cells, the CCK2 receptor. These aptamers have been used to target CPSNPs specifically to tumor cells - CCK2R-specific targeting aptamers enhance the delivery of therapeutic cargos into tumors in vivo. In addition to delivering chemotherapeutic compounds for treatment of pancreatic tumors, these CCK2R-aptamer targeted CPSNPs can also encapsulate imaging agents for early detection of pre- cancerous lesions.

Another characteristic of pancreatic tumors is dense, fibrotic stroma that limits diffusion of therapeutic and imaging agents into tumors. Her research group has characterized a small molecule antagonist of the CCK2R, proglumide, which reduces tumor fibrosis in mouse models of pancreatic cancer. On-going studies combine proglumide with a standard of care chemotherapy drug for pancreatic cancer, gemcitabine, to determine if proglumide-mediated fibrosis reduction enhances the efficacy of gemcitabine.

Finally, the Matters research group examines how cancer cells communicate with other cells within the tumor microenvironment (TME) to enhance tumor progression. Small vesicles known as exosomes are secreted by cancer cells and fuse with other cells in the TME such as macrophages. Exosomes from AsPC-1, an ascites-derived human PDAC cell line, contained much higher levels of the bioactive lipid arachidonic acid (AA), and fused at a higher rate with macrophages than did exosomes from other PDAC cell lines. Furthermore, macrophages treated with AsPC-1 exosomes had significantly increased secretion of pro-tumoral bioactive molecules. These results demonstrate that tumor cell exosomes alter macrophage functions in ways that contributes to tumor progression.