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.