New study below [1].
Foreign terms & acronyms are a massive turnoff for some, but the idea behind the new study is quite elegant & possibly very important.
PTEN.
PTEN is a tumor suppressor gene & is often silenced in PCa.
MYC.
MYC is a regulator gene that is sometimes over-expressed in PCa. As such, it upregulates the expression of genes involved in proliferation.
PTEN loss & MYC gain.
This combination is bad news.
In theory, one would expect to see very high rates of protein synthesis in such an aggressive combination. It turns out that there is less. The reason is that uncontrolled protein synthesis would create an unacceptable level of toxicity in the cells, so the cancer triggers the ‘integrated stress response’, which inhibits a key player in protein synthesis: eIF2.
University of California, San Francisco, had already created a drug that could remove the block on eIF2: ISRIB. A decrease in eIF2 & protein synthesis is associated with memory loss. "In 2013, researchers revealed that a small drug-like molecule, called ISRIB, could prevent this decline in protein production following eIF2" inhibition. "when ISRIB was administered to mice and rats, it enhanced their long-term memories." [2]
"Using patient-derived xenograft models and an inhibitor of P-eIF2α activity, ISRIB, our data show that targeting this adaptive brake for protein synthesis selectively triggers cytotoxicity against aggressive metastatic PCa, a disease for which presently there is no cure." [1]
ISRIB will only work in PCa that has applied the brake to eIF2. This happens in cancer cells where out of control protein synthesis might lead to cell death. Restoring eIF2 levels did indeed cause the PTEN-negative/MYC-positive cells to die in this study.
-Patrick
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