Restoring gene function reverses cancer’s course
Many cancers get their start when the critical tumor suppressor gene, p53, is turned off, setting off a cascade of events in the cell that results in unrestrained growth. Now, in a study from Nature this week, local researchers have shown that restoring the function of the suppressor gene can reverse the process in mice, causing well-established tumors to melt away.
The results indicate that cancers depend on continuous inactivation of the p53 gene to thrive. And since reduced p53 activity is involved in half of all human cancers, methods to reactivate p53 by gene therapy or drug treatment could potentially treat many kinds of cancer.
Normally, the p53 protein keeps cancer at bay by triggering the death of damaged cells before they can grow out of control. The researchers, led by MIT’s Tyler Jacks, genetically engineered mice with a reversible mutation in the p53 gene. With the gene switched off, the mice developed lymphomas and sarcomas. Once they switched the gene on, the tumors disappeared.
This computer-generated 3-D image (based on MRI data) shows an abdominal lymphoma (tumor in red) in a mouse before (left) and 12 days after (right) p53 reactivation. (Credit: Tyler Jacks, Jan Grimm, and colleagues.)
Different cancer types responded differently to p53 reactivation—in lymphoma cells, p53 rapidly triggered cell suicide within just a few days. Sarcoma tumors died more slowly, over a period of weeks, because p53 slowed and then stopped cell division.
A related paper by New York researchers, also published in Nature this week, showed that p53 reactivation similarly inhibited the growth of liver cancer cells, which were then destroyed by the animal’s immune system.
Restoring the function of the p53 gene had no effect on the mouse’s normal tissues, suggesting that p53-based therapies may avoid some of the side effects of traditional cancer treatments such as chemotherapy. Pat McCaffrey
Drug-resistant viruses could spread with flu
Unlike the last flu pandemic, the response to the next one will feature heavy use of antiviral drugs, mainly oseltamivir (Tamiflu). Governments are stockpiling the drugs in anticipation of a major outbreak, but there’s been little public discussion about the problem of resistance that will surely emerge once the drugs are widely used.
In a paper this week in PLoS Medicine, Harvard School of Public Health researcher Marc Lipsitch and colleagues report the results of computer modeling of the impact of drug-resistant flu strains in a worldwide epidemic.
Their results predict that resistant viruses will spread quickly in response to drug use, and their proliferation will reduce the effectiveness of the treatments. Using antiviral drugs will still help delay the spread of the pandemic and reduce its size, though not as effectively as currently predicted. This delay is critical to give extra time for vaccine production in the early stages of the pandemic.
The theoretical scenario makes assumptions about the rates of viral spread, the extent of drug use, and the implementation of other measures like quarantines, school closings, and limits on travel.
One outstanding question is whether drug-resistant viruses will be weaker and less able to pass from person to person, a situation that could improve the effects of therapy.
The bottom line, according to the researchers, is that future planning efforts will need to consider the risk of resistance, and establish procedures for monitoring its emergence during an actual outbreak. Pat McCaffrey
Supernova remnants are missing their halos
When stars blow up in massive explosions called supernovas, much of the star’s mass billows out in a huge cloud, while the center often collapses to form a new star. Astrophysicists have long believed that these new stars are surrounded by a disk of dust.
But a search for these “fallback disks,” using ground telescopes and an orbiting space telescope, has come up empty, according to a new study in the Astrophysical Journal from MIT.
Fallback disks would have implications for the fate of the new star. If the star’s gravity is sufficient to attract the dust, the star could gain enough mass to become a black hole. If the dust stays put, however, it could congeal to form new planets. But if no dust is present, new black holes or planets would be less likely to form than previously thought.
Current computer models of supernovas generally predict the creation of fallback disks, so with little evidence of their existence, astrophysicists may have to revisit their models. Mason Inman
