miércoles, 7 de marzo de 2012

Study Details Cancer-Promoting Activity of mTOR Protein ► NCI Cancer Bulletin for March 6, 2012 - National Cancer Institute

NCI Cancer Bulletin for March 6, 2012 - National Cancer Institute

Study Details Cancer-Promoting Activity of mTOR Protein

The 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.

Also in the News: Judge Rules against Graphic Warnings on Cigarette Packages
U.S. District Judge Richard Leon ruled last week that the Food and Drug Administration (FDA) regulation requiring cigarette packages and displays to carry graphic warnings of the consequences of smoking violated tobacco companies’ free speech rights under the First Amendment. The same judge temporarily blocked the regulation last fall. The government has appealed that decision and will have 60 days to appeal the new decision.
The FDA rule was scheduled to take effect this fall but is now on hold pending the outcomes of the government’s appeals. The Department of Health and Human Services, under which the FDA falls, released a brief statement that read: “This Administration is determined to do everything we can to warn young people about the dangers of smoking, which remains the leading cause of preventable death in America. …We are confident that efforts to stop these important warnings from going forward will ultimately fail.”

Also in the Journals: Questioning the Use of Progression-Free Survival as a Clinical Trial Endpoint
A comment paper published in the Journal of Clinical Oncology last week argues that the cancer research community should consider more carefully the use of progression-free survival (PFS) as an endpoint in clinical trials. Drs. Christopher Booth and Elizabeth Eisenhauer of the National Cancer Institute of Canada noted that growing numbers of trials are using PFS as an endpoint and that drugs are being approved based on the results of such trials.
Although PFS is easily measured, it is unclear whether an improvement in PFS signals improvement in overall survival or quality of life, the authors wrote, leading them to question whether using PFS merely lowers the bar for approving new drugs without real benefit for patients.
See also: “Progression-free Survival: Patient Benefit or Lower Standard?

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