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.
