The metalproteinases are a family of enzymes whose main function is the degradation of extracellular matrix proteins such as collagen, laminin, fibronectin, elastin and proteoglycans of the protein. The MMPs are overexpressed in several malignancies and their overexpression correlates with tumor aggressiveness and metastatic potential. Given that matrix metalproteinases play a key role in the process of neoplastic progression of the disease, as confirmed by data from preclinical and clinical, pharmacological inhibition of the activity of metalproteinases can consequently cause a marked reduction invasiveness of primary tumors and metastases. The family of metalproteinase inhibitors includes several drugs, Marimastat, batimastat, BAY 12-9566, BMS-275291 and bisphosphonates. All except the latter, are still under development both in Italy and abroad. Bisphosphonates, in fact, are already marketed in Italy and represent a class of drugs initially used for the treatment of disorders of calcium and, more recently, for the palliation and prevention of bone metastases in cancer patients. Besides having an effect in preventing skeletal complications in cancer patients with bone metastases, bisphosphonates also seem to have direct antitumor activity. The mechanisms of action responsible for antitumor activity of bisphosphonates are not fully understood yet. Among these we include:
- the ability to induce apoptosis
- the inhibition of tumor cell invasion and the invasion of extracellular matrix of bone.
- anti-angiogenic activity.