Proteinase optical imaging tools for cancer detection and response to therapy

A variety of physiological processes such as wound healing and tissue remodeling are mediated by a plethora of proteinases – enzymes that can hydrolyze peptide bonds – of which as many as 622 have been identified in the human genome. These proteinases are classified into five of the seven clans of peptidases with known catalytic type: S (serine), C (cysteine), A (aspartyl), M (metallo), and T (threonine) [MEROPS, http://merops.sanger.ac.uk; (Rawlings et al. 2008) (Fig. 1)]. In many physiological processes, the proteinases mediate and/or regulate both intercellular signaling, such as in the release and/or processing of chemokines, and intracellular pathways, such as in the apoptotic pathways leading to programmed cell death. Dysregulation of the temporal and/or spatial co-ordination of these intracellular and/or intercellular pathways disrupts the normal physiology and rhythm of life that can be manifest in unregulated growth such as occurs in tumors and their metastatic progeny.