Cancer Drug Discovery and Development
A significant amount of clinical research has been conducted with small molecules that inhibit matrix metalloproteinases (MMP), metal-containing enzymes that degrade the extracellular matrix and are implicated in tumor progression and angiogenesis (1–3). The majority of matrix metalloproteinase inhibitors (MMPIs) are designed with a concept similar to protease inhibitors used in the treatment of acquired immunodeficiency syndrome. MMPIs are currently under development for the treatment of a variety of diseases most notably cancer (3). Unlike conventional chemotherapy or radiation therapy, MMPIs are expected to slow tumor growth and prolong survival without causing detectable shrinkage of tumors. Because MMPIs are predicted to slow tumor growth but not shrink tumors, clinical development is not guided purely by objective tumor responses; proving the therapeutic value of these molecules will therefore require randomized placebo-controlled trials with assessment of the impact of drug treatment compared to placebo. Proof that these compounds are effective cytostatic agents will require demonstrating a survival advantage when compared to a placebo in a randomized, controlled trial.
KeywordsClin Oncol Slow Tumor Growth Metastatic Pancreatic Cancer Matrix Metalloproteinase Inhibitor Blood Vessel Invasion
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