Recent Advances in ADAM17 Research: A Promising Target for Cancer and Inflammation.

Since its discovery, ADAM17, also known as TNF alpha converting enzyme or TACE, is now known to process over 80 different substrates. Many of these substrates are mediators of cancer and inflammation. The field of ADAM metalloproteinases is at a crossroad with many of the new potential therapeutic agents for ADAM17 advancing into the clinic. Researchers have now developed potential drugs for ADAM17 that are selective and do not have the side effects which were seen in earlier chemical entities that targeted this enzyme. ADAM17 inhibitors have broad therapeutic potential, with properties ranging from tumor immunosurveillance and overcoming drug and radiation resistance in cancer, as treatments for cardiac hypertrophy and inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. This review focuses on substrates and inhibitors identified more recently for ADAM17 and their role in cancer and inflammation.