The Proteases in Cancer Laboratory of Evette S. Radisky, Ph.D., at Mayo Clinic investigates proteases implicated in several types of cancer. Research in the Proteases in Cancer Laboratory focuses on the molecular interactions involved in inhibiting these proteases, employing techniques of structural biology, cell biology, enzymology, protein engineering and directed evolution.
A crucial step in tumor development is the invasion of surrounding tissues, a process that can lead to development of distant metastases. Tumors accomplish this through increased activity of enzymes that degrade the proteins connecting the cancer cells to each other as well as the structural elements of the extracellular matrix. In the microenvironment of normal tissues, proteolytic activity is modulated by endogenous inhibitors that bind to and inactivate proteases; in malignant tumors, the delicate balance between production, activation and inhibition of proteases is often disturbed, leading to tumor cell invasion and dissemination.
Different forms of cancer show increased activity of specific proteases and decreased activity of the opposing endogenous inhibitors; identification of these altered interactions provides a handle for therapeutic intervention. Through studying the natural interactions between these enzymes and their endogenous inhibitors, the Proteases in Cancer Laboratory hopes to design better agents for blocking tumor invasion and metastasis.