Recent Advances in Mesothelioma Research Target Proteins within the Body

Science Daily reported on two recently published studies which both focus on therapies for mesothelioma that target the protein p53 within the body. P53 is responsible for regulating cell growth and the repair of damaged cells, but becomes inactive in most human cancers due to alterations in its pathway.

The first study was lead by pathologist Antonio Giordano, Director and Founder of the Sbarro Health Research Organization in Philadelphia, Pennsylvania, and Professor of Pathology and Oncology at the University of Siena, Italy. The researchers used a drug called RITA with another drug, both designed to reactivate p53 which is vital for tumor suppression. The drug combination proved to be very toxic to the mesothelioma cells, but not to healthy cells. The researchers also found that the RITA combo worked synergistically with cisplatin, the most common chemotherapy drug used to treat mesothelioma.

The RITA combination induced apoptosis (cell death) in epitheloid mesothelioma cell type cell lines, but the more aggressive sarcomatoid cell type of mesothelioma was not responsive. "It remains to be seen whether the combination of RITA with other activators of apoptosis can achieve efficacy also against the more aggressive cases," says Alfredo Budillon, Head of the Experimental Pharmacology Unit of the National Cancer Institute of Naples and coauthor of the study.

The second study was led by Paola Indovina of the University of Siena and the Sbarro Institute for Cancer Research and Molecular Medicine, Temple University in Philadelphia. In this study the researchers tested a new drug called MK-1775, which is currently being tested in clinical trials for other types of tumors, in combination with cisplatin designed to inhibit the protein WEE1 which is crucial in the process of repairing damaged DNA before cells divide. This study also focused on the protein p53, when p53 is inactive due to the presence of cancer cells, the WEE1 protein allows cancer cells to repair themselves after exposure to genotoxic agents like chemotherapy drugs. When MK-1775 inhibits the WEE1 protein, it allows the cisplatin to interrupt a crucial step in the cancer cell division process. The damaged cancer cells are still able to divide, but experienced apoptosis as a result of the interruption.

Mesothelioma is a particularly aggressive cancer, by attacking the mechanisms that allow the rapid growth and spread of the disease within the body it will hopefully reduce the extremely high rate of recurrence and give patients a better prognosis and quality of life. 

Study Involving New Chemotherapy Combination Shows Improved Results Over Cisplatin for Pleural Mesothelioma

To date, chemotherapy drugs used to treat mesothelioma have primarily included cisplatin, onconase, carboplatin, gemcitabine, navelbine and pemetrexed (Alimta). In some cases, these medications have been noted to stall the progression of mesothelioma tumors. Chemotherapy, however, has been shown to be most effective when combined with surgery, radiation, or other treatment modalities, known as multi-modal treatment.

Since 2004, the only chemotherapy regimen which the FDA has approved for pleural mesothelioma is cisplatin and Alimta. The approval, however, is limited to patients who are not surgical candidates.

A recent European study has monitored the results of cisplatin used in combination with a drug called Tomudex (raltitrexed) for pleural mesothelioma. The study has shown improved median survival rates for patients on the cisplatin-Tomudex combination as compared to cisplatin alone.

Tomudex is an injectable cytotoxic medication used to treat different forms of cancer. The medication belongs to a group of cancer-fighting drugs called antineoplastics. Tomudex combats cancer by preventing cancer cell growth, which in time leads to their elimination.

In the study, one group was treated with cisplatin alone and another group was treated with both cisplatin and Tomudex. The overall response rate for the cisplatin-Tomudex group was higher than the cisplatin group, 23.6 percent and 13.6 percent, respectively. Tomudex was shown to improve median overall survival by 2.8 months and Tomudex was associated with improved progression-free survival.

Professor J.P. van Meerbeeck (professor of Thoracic Oncology at Ghent University, Belgium) said, “Malignant pleural mesothelioma is a hard to treat, rare cancer with a poor prognosis. New treatment options such as a combination of cisplatin and raltitrexed, which improve patient outcomes with no detrimental effect on quality of life as compared to cisplatin alone are a welcome addition to our therapeutic portfolio.”

Tomudex is currently licensed for the treatment of pleural mesothelioma in Portugal, Czech Republic and Hungary. Additional licensing is expected across Europe in late 2010.

Please check back with Mesothelioma Bytes for future updates on the testing and approval of Tomudex in the treatment of mesothelioma.