Clapper, Patti, Schweizer and Mason

A recent report from Japan reports that the NK4 agent can suppress cell proliferation and prevent tumor growth in patients diagnosed with malignant pleural mesothelioma, a rare and aggressive cancer caused by exposure to asbestos.  The research from Osaka University, published in the International Journal of Cancer last month, provides new insights into understanding and treating mesothelioma.

NK4 is an agent that inhibits the Met/HGF receptor and causes angiogenesis, which slows tumor growth and interferes with migration of malignant mesothelioma cells.  In mesothelioma, MET contributes to invasive growth through overexpression and activates increased drug resistance.  Tumors may also show alterations of the MET gene.  Molecules or agents that target MET can block signaling causing suppression of cancer cell growth and metastases.   Therefore MET inhibitors, such as NK4, are being researched as therapies against mesothelioma cancer.

The study from Japan showed that NK4 inhibits the hepatocyte growth factor (HGF) through binding to the Met/HGF receptor as well as creates an antiangiogenic action through binding to perlecan.  Anti-angiogenesis is a type of targeted therapy that uses drugs or other agents to stop tumors from making new blood cells, thereby causing tumor and malignant cell death.  Cancer cells survive and grow through use of the blood vessels, so blocking off supply causes tumors to shrink and cancer cell death.  Perlecan consists of a core protein and is a major heparin sulfate proteoglycan (HSPG) of basement membranes and connective tissues.  Understanding the molecular attributes of perlecan, which research shows to be involved in tumor cell proliferation, may offer insight into therapeutic interventions for mesothelioma. 

NK4, a known HGF/SF antagonist, was shown to interfere with the development of new blood vessels, significantly reducing invasiveness and motility of mesothelioma cells.  Tumor size and growth was decreased enough to indicate NK4 as an agent worthy of further therapeutic inquiry.  NK4 has already proven to be effective at treating other cancers, such as breast, pancreatic, gall bladder, and other types of lung cancer not related to asbestos exposure.