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.