Researchers Offer Hope That Chemo-Resistance in Mesothelioma Can Be Overcome
Malignant Peural Mesothelioma (MPM), an aggressive, asbestos-related cancer found in the outer lining of the lungs called the mesothelium, is often resistant to standard cancer treatments, including chemotherapy, leaving patients with few treatment options and a poor prognosis. Now, researchers at Fox Chase Center have identified a protein, Abcc10 (also known as Mrp7), that causes the body to resist certain drugs used to treat cancers including breast, lung and mesothelioma. The researchers say the findings “suggest that blunting the activity of Abcc10 might help counter resistance and extend the effectiveness of these anticancer drugs.”
Treatment for pleural mesothelioma and non-small cell lung cancer is often similar, with chemotherapy being one of the primary treatment modes. Paclitaxel and carboplatin are two of the primary chemotherapy agents used in treating lung cancer. Currently, the combination of gemcitabine and cisplatin is one of the most common chemotherapy treatments for mesothelioma patients, however, other newer drugs, including paclitaxel, now are often preferred and are usually given in different combinations to mesothelioma patients.
In a previous study, Elizabeth A. Hopper-Borge, PhD, an assistant professor at Fox Chase and the lead researcher in the current study, showed that Abcc10 is the cause of chemo-resistance in some patients being treated with anticancer agents known as taxanes, including paclitaxel (Taxol).
In order to further test the effect of Abcc10, the research team developed a “knockout” mouse, in which the gene that codes for Abcc10 was missing, or knocked out. Since the mice were normal and healthy without the presence of Abcc10, the researchers discovered that the protein is not essential for survival.
The researchers isolated cells from the knockout mice to test their reaction to taxanes, including paclitaxel and two other anticancer drugs. The tests found that compared to cells from normal mice that still possessed the gene for Abcc10, the knockout mouse cells were much more sensitive to the drugs, meaning that they no longer had a resistance to the drug.
The researchers concluded that “Abcc10 is a cell’s built-in protection against the effects of powerful drugs, and raises the possibility of using Abcc10 inhibitors to break down that resistance and sensitize tumor cells to anticancer agents.”
Hopper-Borge is mindful that the tests were conducted on mice, saying, “Our results so far suggest that this protein may be a clinically relevant target, but we need to do more studies to find out for sure.”
The research was supported by the National Institutes of Health.
Fox Chase Center is an NCI-designated comprehensive cancer center, offering treatment for lung cancer, including complex cases, cancer recurrence, and inoperable lung cancer. Physicians at Fox Chase offer treatment for: small cell lung cancer, non-small cell lung cancer, mesothelioma, pleural disease and thymoma.
