Jun 20, 2012 - Gene Therapy for Mesothelioma Targets Inhibitory Protein 1 Promoter System
Because traditional cancer therapies such as chemotherapy and radiotherapy only have limited results at best when used as a mesothelioma treatment, researchers have pinpointed “an urgent need for new therapeutic options for mesothelioma.” One of these new “out-of-the-box” approaches such as gene therapy and virotherapy (using modified viruses to combat the cancer) should be more fully explored. Recent research from Japan exposes one possible pathway in which scientists could combat mesothelioma through a specific Inhibitory Protein 1 Promoter System.
Specifically the new method of approach would target the promoter of the CREBBP/EP300 inhibitory protein 1 (CRI1). This gene is specifically expressed in malignant pleural mesothelioma cells and could be used as an effective target at which to fire new anti-cancer treatments.
The Japanese scientists discovered that four tandem repeats of the CRI1 promoter gene caused significantly higher activity in malignant pleural mesothelioma cells but did little to change the status of promoter activity in normal, non-cancerous mesothelial cells and normal non-cancerous fibroblasts. This is important because one key aspect of any future mesothelioma treatment would be to target the cancerous cells specifically while minimizing the impact to other, healthy cells.
Acting with this genetic mechanism as a funnel through which they focused their attack, the Japanese team used a recombinant adenoviral vector, a genetically modified virus, that caused cell death in the malignant mesothelioma cells. The treatment was extremely effective and researchers were able to ramp up the experimentation and demonstrate antitumor effects in cancerous mouse tissues.
This area of experimentation is not new. The first gene therapy trial approved for use on humans in the United States was created specifically to combat mesothelioma. Since then, three other trials have attempted different avenues of attack against this aggressive and lethal cancer. However, none of these clinical trials for mesothelioma showed any promise.
Scientists continue to look for a better approach. To that end, the Japanese team examined the promoters of four different mesothelioma-specific genes:
- Salretinin
- Wilms' tumor suppressor gene
- Mesothelin
- CREBBP/EP300 inhibitory protein 1
They zeroed in on this fourth option because all of the other gene promoters showed high levels of activity in non-cancerous cells whereas the CREBBP/EP300 inhibitory protein CRI1expressed high levels of activity specifically in malignant mesothelial cells. In other words, all of the other possible genes they examined were too broad to allow for effective treatment. Any sort of genetic or viral therapy targeting those specific genes would damage healthy cells as well.
To satisfy the wide-ranging need for this type of treatment, researchers examined a large sample of mesothelioma cells from a variety of sources. These tissue samples were then subject to viral therapy with a specifically modified adenovirus. During the experiments, scientists noted cell death in a high percentage of the samples – the virus was killing the mesothelioma cells. To rule out possible errors or fluke results, they repeated the individual experiments at least two more times. The results were the same.
Building on the success they had with the in vitro (laboratory) experiments, the team moved onto experimentation in mice. This is where they saw the antitumor results such a targeted viral attack which led them to suggest that this type of combined gene and viral therapy may indeed be an effective way to treat mesothelioma in human patients as well.
The Japanese team is hopeful that the antitumor and anticancer results they observed in mice may be replicated in humans who are suffering from asbestos cancer and related diseases.
Back to Treatment Research Listing