'Beautiful scientific work'
In the new study, Conn and her team administered ISRIB to mice with prostate cancer. They also tested it on human prostate cancer cell lines in vitro.
The results were promising; the molecule restored a high rate of protein synthesis in aggressive cancer with combined genetic mutations, thus exposing them to sustained cellular stress and triggering apoptosis, or cell death.
Also, the researchers saw that ISRIB did not affect healthy cells surrounding the cancerous tissue.
The team then conducted some experiments on mice that received transplants of human prostate cancer tissue — a process known as "patient-derived xenografts."
They found that the animals who received samples of aggressive tumors — with the MYC/PTEN mutations — responded very well to ISRIB, and their tumors shrank drastically.
Mice that received less aggressive prostate cancer tumor grafts only experienced a temporary slowing of tumor growth.
"Together these experiments show that blocking P-eIF2a signaling with ISRIB both slows down tumor progression and also kills off the cells that have already progressed or metastasized to become more aggressive," Conn explains.
And co-author Peter Carroll adds, "This is beautiful scientific work that could lead to urgently needed novel treatment strategies for men with very advanced prostate cancer."