The spread or metastasis of cancer is ultimately responsible for most cancer deaths. New drugs employing unique mechanisms are needed to improve therapy of these advanced cancers. New biologic treatments based on functional changes in the extracellular matrix during cancer progression represent a novel approach. TIMPs are a small family of low molecular weight proteins first identified as endogenous metalloproteinase inhibitors. However, these proteins also modulate growth, migration and invasion of both normal and tumor cells. TIMP-2 inhibits tumor growth and metastasis in animal models independent of its protease inhibitor activity. TIMP-2 is under development as a new biologic therapy for cancer.