Published on December 14, 2013 at 9:58 AM
Fisher and his team identified an existing combination of receptors, IL-20R1 and IL-20R2, and a discovered new combination of receptors, IL-22R1 and IL-20R1, through which signaling occurs to induce the MDA-7/IL-24 autocrine/paracrine loop. Once activated by the MDA-7/IL-24 protein, these receptors cause both normal and cancer cells to produce and secrete the MDA-7/IL-24 protein, which, in turn, activates SARI. The process was shown to culminate in apoptosis in cancer cells. Normal, healthy cells were not affected in the experiments.
The researchers are now focusing on developing small molecule drugs that induce MDA-7/IL-24 and/or SARI in cancer cells. They have also been experimenting with cancer-selective replicating viruses that seek out cancer cells and infect them with the toxic genes-an approach that has already been successfully employed in a phase 1 clinical trial using engineered viruses that deliver MDA-7/IL-24.
"This study helped us better understand how MDA-7/IL-24 works to kill a broad range of cancer cells through the induction of SARI," says Fisher. "In addition to giving us another target for the development of new therapies, our research also suggests that we may be able to monitor the expression of SARI in order to determine the effectiveness of future therapies under development that target MDA-7/IL-24."
Source: Virginia Commonwealth University