Clapper, Patti, Schweizer and Mason

PLX3397, a novel agent designed to attack tumor cells, has been used in preclinical trials involving several types of cancer including mesothelioma and has shown impressive results.  The agent, manufactured by Plexxikon Inc., a member of Daiichi Sankyo Group, is designed to radically alter the cancer tumor’s microenvironment and promote cell destruction and tumor reduction. 

PLX3397 is orally administered and is engineered to be used in single agent treatment applications.  It is specifically tweaked to alter macrophages and osteoclasts.  These two types of cells enable certain types of cancer to undergo metastases and attack other areas of the body including bone.  However, because of the effectiveness of PLX3397, researchers have noted that tumors in patients with certain types of cancer have actually diminished significantly when treated. 

Indeed, Dr. Gideon E. Bollag, senior vice president of Plexxikon, states:  “we have generated a significant set of preclinical data supporting the advancement of PLX3397 as a potential treatment for cancers in which the tumor microenvironment plays an essential role.”  So promising are these results that Plexxikon scientists have decided to expand the use of this novel new agent to other types of cancer including prostate cancer.

However, it is the work with malignant mesothelioma cells that has shown some of the most impressive results.

Mesothelioma is a preventable form of cancer that strikes nearly 3,000 people in the United States every year.  Caused by the inhalation or ingestion of asbestos fibers, mesothelioma tumors are notoriously resistant to treatment, aggressive in nature, and significantly decrease a patient’s expected life span.  To date, scientists have been unable to find an effective mesothelioma treatment that does not adversely affect normal bodily functions.

Dr. Lisa Coussens conducted a study at the University of California specifically looking at how PLX3397 affected mesothelioma tumors.  She found that after being treated with this novel new agent, mesothelioma cells suffered greatly.  Not only did they exhibit increased tumor cell death, the size of the overall tumors decreased as well.  This result was partially due to the reduction of macrophages and increase in cytotoxic T-cell infiltration. 

T-Cells, a form of lymphocyte, are produced by the body’s immune system and attack foreign invaders.  Mesothelioma is particularly resistant to T-cells but PLX3397 has been shown to decrease that resistance meaning that a patient’s own immune system can now aid in the fight against the mesothelioma tumor. 

Based on these results, Plexxikon has proceeded with Phase 2 clinical trials involving Hodgkin lymphoma and is currently planning studies with other types of cancer including acute myelogenous leukemia, metastatic breast cancer, and prostate cancer.