Preclinical assessment of fibroblast activation protein as a target for antitumor therapy

Evaluation of: Santos AM, Jung J, Aziz N, Kissil JL, Pure E: Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice. J. Clin. Invest. 119(12), 3613-3625 (2009). Many human tumors develop a stromagenic response, involving activation of myofibroblasts, increased angoigenesis and changes in extracellular matrix deposition. Increased expression of the cell surface type 11 transmembrane serine protease fibroblast activation protein has previously been noted in such tumor-associated reactive stroma. The potential for stroma to modify tumor progression, both positively and negatively, has been experimentally demonstrated, although the underlying mechanisms are still only partially understood. Current developments in our understanding of stromal responses to tumors are starting to open the door to therapeutic approaches aimed at the stroma. This study by Santos et al, examines the role of stromagenic response-associated fibroblast activation protein in tumor growth and demonstrates that inhibition of peptidase activity might be a reasonable approach with which to slow the growth of some tumors.