Scientists have been testing new molecules that inhibit kinase SRC effectively inducing cell death by apoptosis, only lines with mesothelioma. Researchers at the laboratory of Antonio Giordano, MD, Ph.D., founder and director of Sbarro Institute for Cancer Research and Molecular Medicine, have identified new potential anti-cancer agents that may be effective in the treatment of mesothelioma, one of most deadly cancers caused by asbestos exposure.
Scientists have been testing new molecules such as pyrazolo [3.4-d] pyrimidine inhibiting SRC kinase, an established molecular target in cancer therapy. Researchers have shown that these inhibitors effectively SRC induce cell death by apoptosis, specifically in mesothelioma cell lines and show no toxic effects on normal mesothelial cell lines, thus supporting a possible use of these agents for the reliable mesothelioma.
These results were published in the journal Oncogene the Nature Publishing Group. The researchers also found that SRC inhibitors induce an increase in the nuclear stability of the cyclin-dependent kinase inhibitor p27.
This is “particularly interesting when you consider that the loss of nuclear expression of p27 is a known negative prognostic factor in mesothelioma and nuclear localization of p27 is critical for its tumor suppressor function,” said the study’s lead author, Dr. Paola Guess, University of Siena and assistant professor at the Sbarro Institute.
“We think that these data represent a timely contribution, and suggest that p27 status should be carefully analyzed to evaluate the use of SRC kinase inhibitors in clinical trials for mesothelioma patients,” said study leader Dr. the ssa Francesca Pentimalli, National Cancer Institute “Fondazione Pascale” – CROM-Cancer Research Center in Mercogliano and assistant professor at the Sbarro Institute.
“The results confirm the fundamental SRC as a therapeutic target in mesothelioma and reveal a new mechanism, dependent on nuclear stabilization of p27, through which the inhibition of SRC can induce apoptosis in mesothelioma cell lines, providing a new rationale for the use of SRC inhibitors in the treatment of this cancer, “says Prof. Antonio Giordano. This also shows that in this context, p27 is required to induce apoptosis in mesothelioma cell lines and, although this mechanism has yet to be defined precisely, it identifies an active role of p27 in mediating apoptosis”.
The study was conducted in collaboration with Prof. Maurizio Botta, Professor of Pharmaceutical Chemistry and Dean of the Faculty of Pharmacy, University of Siena and also Adjunct Professor at the Sbarro Institute, who developed these inhibitors together with Prof. SRC Silvia Schenone University of Genoa, Italy.
