An altered form of a virus that typically causes respiratory illness may help boost the effectiveness of chemotherapy for mesothelioma.
In a study published in the Journal of Thoracic Oncology, researchers found that deleting a gene from adenoviruses made the drugs pemetrexed and cisplatin more cytotoxic to mesothelioma cells in the lab.
In its unaltered state, the adenovirus is the virus most closely associated with respiratory problems, ranging from the common cold to pneumonia, croup and bronchitis. It can also cause gastroenteritis, cystitis, and conjunctivitis. However, when it is altered in the lab by removing a particular gene, it can become a powerful ally in the fight against hard-to-treat cancers like mesothelioma.
In the latest study, researchers first deleted the E1B-55kD gene from adenoviruses and then exposed the altered viruses (expressed as Ad-delE1B55) to mesothelioma cells along with a combination of pemetrexed and cisplatin. They found that the virus “produced antitumor effects in vitro.” But even more exciting was the fact that the virus also increased the cytotoxicity of cisplatin against mesothelioma in an orthotopic animal model.
According to the study’s authors, the Ad-delE1B55 appears to work by interfering with the life cycle of mesothelioma cells, stimulating programmed cell death (apoptosis) to occur earlier and making them more vulnerable to the cytotoxic effects of first-line chemotherapy drugs. Examination of the treated mesothelioma cells also found chromosomal abnormalities. Finally, Ad-delE1B55 appeared to turn on the p53 tumor suppressor gene, which is often defective in mesothelioma patients. The study summary concluded that “…the oncolytic adenovirus is a potential therapeutic for mesothelioma”.
There are few effective therapeutics for mesothelioma, a rare but aggressive malignancy caused by exposure to asbestos. Studies aimed at improving the effectiveness of chemotherapy are vital since chemotherapy alone does not usually give mesothelioma patients more than a few extra months of life. Several other compounds, including COX-2 inhibitors, have also been shown in some studies to improve the effectiveness of chemotherapy.