Study Details Cancer-Promoting Activity of mTOR ProteinThe mTOR protein, a regulator of protein translation that is overactive in many cancers, increases the production of a specific group of proteins that help cancer cells escape tumors and invade other tissues, according to a new study published online February 22 in Nature. The same study found that, in mouse models of metastatic prostate cancer, an investigational drug called INK128 that potently blocks mTOR’s activity shrank tumors and prevented metastasis more effectively than other mTOR inhibitors.
Because of its mechanism of action, INK128 and other drugs in development that target mTOR in a similar way may be particularly effective in treating metastatic disease, noted the study’s lead investigator, Dr. Davide Ruggero of the University of California, San Francisco.
Using a new technique called ribosome profiling that shows which messenger RNAs are being translated into proteins by the ribosomes in a cell, the research team pinpointed a group of four proteins—all of which cluster together in a signaling “node”—in advanced prostate cancer cell lines whose translation was altered by mTOR inhibition.
The technology, Dr. Ruggero explained, allows researchers to analyze what is happening at the functional level in cells, particularly the production of proteins, which are the primary drivers of cellular activity. “These four proteins were really most affected downstream [of mTOR] at the translational level,” he continued. “And we show, one by one, their functional role in making tumor cells more metastatic or more invasive.”
In the mouse models, “treatment with INK128 completely blocked the progression of invasive prostate cancer locally in the prostate gland, and profoundly inhibited the total number and size of distant metastases,” the study authors wrote.
Several study authors are from the California-based company Intellikine, which is developing INK128. The drug is being tested in several phase I trials.