Mesothelioma is a very aggressive cancer associated with asbestos exposure, which is usually diagnosed in an advanced stage. So far no therapeutic strategy has proven effective against this deadly cancer and the prognosis remains very poor with only few exceptions.
In December, the research team of Antonio Giordano, an internationally renowned pathologist, Director and Founder of the Sbarro Health Research Organization in Philadelphia, PA (www.shro.org) and Professor of Pathology and Oncology at the University of Siena, Italy, published two separate studies aiming to address the urgent need to identify possible new methods for mesothelioma treatment.
In the first study, published in the scientific journal Cell Cycle, Giordano's researchers tested on mesothelioma cells the effect of two drugs designed to reactivate the p53 protein, one of the most important 'tumor suppressors', which is turned off in most human cancers. "In mesothelioma, although p53 is rarely mutated, it is inactivated by alterations in its pathway," says Francesca Pentimalli of the National Cancer Institute of Naples, Italy, lead author of the study. Both of the drugs used in the study target p53, but with different mechanisms of action. One in particular, called RITA, proved to be very toxic. Specifically, RITA caused mesothelioma cells, and not 'healthy' cells, to undergo apoptosis — a type of programmed cell death that occurs through the activation of a specific 'cascade' of events.
"The ability of RITA to induce apoptosis is remarkable considering that mesothelioma is very refractory to this process. In fact the most aggressive and rare variant, sarcomatoid mesothelioma, did not respond to the treatment probably because of its intrinsically high levels of molecules acting as inhibitors of this process" says Alfredo Budillon, Head of the Experimental Pharmacology Unit of the National Cancer Institute of Naples and coauthor of the study. "It remains to be seen whether the combination of RITA with other activators of apoptosis can achieve efficacy also against the more aggressive cases."