Combined Radiochemotherapy: Metalloproteinases Revisited

Besides cytotoxic DNA damage irradiation of tumor cells triggers multiple intra- and intercellular signaling processes, that are part a multilayered, treatment-induced stress response at the unicellular pathophysiological level. These processes intertwined with intrinsic acquired resistance mechanisms to toxic effects ionizing radiation thereby co-determine radiotherapy. Proteolysis structural elements bioactive moieties represents major class posttranslational modifications regulating communication. Plasma membrane-located secreted metalloproteinases comprise family metal-, usually zinc-, dependent endopeptidases sheddases broad variety substrates including components extracellular matrix, cyto- chemokines, growth pro-angiogenic factors. Thereby, play an important role in matrix remodeling auto- paracrine communication growth, angiogenesis, immune cell infiltration, dissemination, subsequently cancer treatment. While have long been identified as promising target structures for anti-cancer agents, previous pharmaceutical approaches mostly failed due unwanted side related similarities among members. Nevertheless, targeting still interesting rationale alone combination other treatment modalities. Here, we will give overview on irradiated microenvironment discuss therapeutic potential using more specific metalloproteinase inhibitors