Harnessing anti-matrix remodeling biological inhibitors to decipher cancer and inflammatory molecular mechanisms

Proteolytic processes in the extracellular matrix (ECM) and on cell surfaces dictate cell behavior and tissue integrity under normal homeostasis and in diseased tissues. These well-coordinated proteolytic events involve versatile enzymes and their physiological substrates. Matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase (ADAMs) and Lysyl Oxidases (LOXs) are sub-families of remodeling enzymes that continuously remodel cell microenvironments, in practically all tissues, through direct proteolysis of ECM proteins or through the release and functional modification of a variety of key cell-surface bioactive molecules. This complexity, combined with the failure of the clinical trials testing MMPs/ADAMs/LOX inhibitors for disease treatment inspired the design of novel anti-matrix remodeling biological inhibitors exhibiting great efficacy in vitro and in vivo. In my talk I will discuss the design of these biological inhibitors as well as the integration of systems biology protocols and biochemical inhibition analyses to decipher novel molecular mechanisms in both cancer and inflammatory microenvironments.