Antimicrobial and non-antimicrobial tetracyclines in human cancer trials.

Tetracyclines are capable of inhibiting mammalian collagenases by non-antimicrobial mechanisms. Because collagenases and other matrix metalloproteinases have been linked to cancer pathogenesis, this property of tetracycline's has led to speculation that these drugs could be used to slow tumor growth, invasion and metastasis in neoplasms that overly express these enzymes. The FDA has already approved two tetracycline derivates for treatment of chronic inflammatory periodontal disease and chronic inflammatory skin disease. Here we review the efforts to determine the efficacy of tetracyclines as chemotherapeutics in human cancer trials. While the majority of clinical trials have yielded disappointing results, tetracyclines have been shown to be generally well tolerated and have significant anti-proliferative effects in certain cancer types. In particular the chemically modified tetracycline derivative COL-3 (also known as CMT-3) has been shown to cause dramatic improvement in the tumor burden of patients with Kaposi Sarcoma. The experience using tetracyclines as chemotherapeutics is relatively limited, but further success is possible if future trials are focused on specific cancer subtypes that are known to rely heavily on collagenases and other matrix metalloproteinases for their pathogenesis.