Mesothelioma is the most deadly of several diseases caused by asbestos exposure, including lung cancer, asbestosis and pleural plaques. Most people who develop mesothelioma live less than a year after diagnosis. It is most common in people who have lived or worked around asbestos.
Although the disease is resistant to most conventional cancer therapies, a new report published by doctors at the Hyogo College of Medicine in Japan and the University of Miami suggests that agents that prevent blood vessel growth, known as angiogenesis, may be more effective.
To test the theory, they introduced angiostatin, endostatin and vascular endothelial growth factor receptor 2 (sFlk1) into human mesothelioma cells in the lab using a lentivirus – a ‘deactivated’ virus that can get through cell walls. When the mesothelioma cells received these anti-angiogenic proteins, they began producing them on their own. Because the approach alters the cells’ genetic code, it falls under the category of gene therapy.
While the individual anti-angiogenic agents prompted the mesothelioma cells to produce more of these proteins, they did not appear to keep the cells from growing and replicating. However, when the proteins were delivered in combination, the researchers report “significant suppression of human umbilical endothelial cell growth.”
“These results suggest that combinatorial anti-angiogenic gene therapy targeting different pathways of endothelial growth factor signaling has the potential for greater therapeutic efficacy than that of a single-agent regimen,” writes lead author Shuji Kubo of the Hyogo College of Medicine.
Like other types of cancer, rapidly growing mesothelioma tumors need a growing supply of new blood vessels to support them. If they fail to produce the proteins that give rise to this blood vessel growth, the tumor’s growth will slow down or stop.
The new research is published in Oncology Reports.
Kubo, S, et al, “Combinatorial anti-angiogenic gene therapy in a human malignant mesothelioma model”, June 12, 2015, Oncology Reports, Epub ahead of print