Most mesothelioma patients will undergo chemotherapy at some point, whether in preparation for surgery or as a treatment by itself. New research conducted in Italy suggests that it may be possible to make that chemotherapy more effective by manipulating proteins in the cancer cells.
Researchers at Salento University in Milan focused on the role of protein kinase C (PKC), a family of enzymes that influence important cellular processes, including the process of apoptosis or programmed cell death. They found that different variations or isoforms of PKCs have different reactions to the popular mesothelioma drug cisplatin, and that those reactions might be controlled.
The theory was tested on a line of human mesothelioma cells grown in the laboratory. The cells were treated with cisplatin at various concentrations and for different lengths of time. The cells were then tested to determine the status of critical proteins and enzymes and to see just how toxic the drug was to them.
According to the researchers, the cisplatin activated one type of PKC which increased the death rate among mesothelioma cells. When this PKC isoform was inhibited by manipulation of the RNA of the cells, cell apoptosis slowed down and the cisplatin was less effective.
On the other hand, another isoform of PKC was found to protect mesothelioma cells exposed to cisplatin. When researchers inhibited this isoform, cisplatin became more toxic to the mesothelioma cells and more of them died.
While the new research is unlikely to lead directly to a new treatment for mesothelioma, it is a step closer to improving patient response to existing treatments. Currently, only a small percentage of mesothelioma patients respond to chemotherapy with the standard drugs pemetrexed and cisplatin. An improved understanding of the molecular reasons for this may allow scientists to develop more effective therapies and, it is hoped, improve survival for the 2,500 Americans diagnosed with mesothelioma each year.
Muscella, A, PKC-δ/PKC-α activity balance regulates the lethal effects of cisplatin, August 20, 2015, Biochemical Pharmacology, Epub ahead of print