They are concentrating their efforts on a protein called TNF-related apoptosis-inducing ligand, also known as TRAIL. TRAIL is a cytokine that is produced by most normal tissue cells but causes apoptosis (programmed cell death) in tumor cells. TRAIL is one of the ways the body helps keeps cancers like mesothelioma from gaining a foothold.
Recently, doctors at the University of Padua ran a test combining a form of TRAIL made from human cells with standard chemotherapy drugs to help fight malignant pleural mesothelioma. The lab-produced TRAIL, called dulanermin, was administered along with pemetrexed and carboplatin to mesothelioma cells in the lab and to live mice with human mesothelioma.
The researchers report a “significant increase of apoptosis” in mesothelioma cell lines treated with the chemotherapy/dulanermin combination. In fact, both in the lab and in the mice, these mesothelioma cells were more responsive to the combination of drugs (which the team labeled CPT) than they were to either chemotherapy or dulanermin alone.
The doctors believe that dulanermin may help block the growth of mesothelioma cell lines by activating certain genes whose job it is to keep cancer at bay. For example, cancer has been shown to proliferate when the tumor-suppressing p53 gene is mutated or inactive. Chemotherapy appears to work synergistically with dulanermin to make cells more sensitive to its apoptotic effects.
“In vitro results suggest that chemotherapy sensitizes malignant pleural mesothelioma to TRAIL-dependent apoptosis through p53 activation and subsequent upregulation of DRs [TRAIL receptors],” writes Giulia Pasello, MD, a medical oncologist and lead author of the study. With more TRAIL receptors, mesothelioma cells are more likely to enter apoptosis.
If additional studies of CPT in animals produce similar results, the next stage would be to test the safety and efficacy of the treatment in human mesothelioma patients.
Source: Pasello, G et al, “Synergistic Antitumor Activity of Recombinant Human Apo2L/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) in Combination with Carboplatin and Pemetrexed in Malignant Pleural Mesothelioma.