Mark FarrellMark Farrell (2017-18)
Assistant Professor, Department of Medicinal Chemistry
University of Kansas

The Inhibition of polysialytransferase ST8Sia II: A novel approach toward the prevention of cancer metastasis

The prevention, inhibition and reversal of cancer metastasis is of upmost importance in order to improve the state of standard of care for cancer patients.The deadliest aspect of cancer is its ability to metastasize – migrate from a primary tumor to multiple distant sites. This is often the final, lethal step in the progression of solid tumors. To metastasize, a tumor cell has to learn to survive independently, enter the blood stream, travel to and recognize a potential new home, leave the blood stream, establish itself in a new setting, invade nearby tissues and attract its own blood supply to allow growth. Although a distinct, complicated, multi-step physiological process with its own dynamics, metastasis has remained largely unexplored and thus poorly understood.

Importantly, each step in this complicated process provides a therapeutic target. This project will investigate the ability of peptide derived small molecules to inhibit the posttranslational polysialylation of the neuronal cell adhesion molecule (NCAM), a glycoprotein which plays a key role in the detachment of cancerous metastatic cell from the primary site of tumorigenesis. In the absence of the polymeric polysialic acid cells expressing NCAM lack the ability to metastasize. Specifically these compounds will be designed to block a key interaction between NCAM and the polysialyltransferase ST8SiaII, which is essential for efficient polysialylation.