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Putting the Brakes on Cancer
by David Cameron
If you can imagine what it's like to be in a car with a stuck gas pedal and no brake fluid, then you can understand the logic of cancer genetics. When members of a class of genes called oncogenes become mutated or altered, cell division shifts into overdrive; and when members of another class called tumor-suppressor genes are damaged, the emergency brake goes limp. As a result of this destructive "perfect storm," the cell goes out of control—and cancer begins.
When they're working well, tumor-suppressor genes fend off cancer in several ways: they halt the cell's ability to grow and divide, and they can press the "self-destruct button" that kills the cell but spares the tissue.
Of all the different tumor-suppressor genes, one in particular, called p53, stands out. p53 is deleted or mutated in roughly half of all human cancers. And although scientists have for years been trying to discover everything they can about this critical gene, one fundamental question had until recently remained unanswered: Do advanced tumors still need to keep p53 turned off in order to spread, or does the gene simply become obsolete as other factors take over? In other words, after a certain point, does cancer care about p53?
HHMI investigators Tyler Jacks of the Massachusetts Institute of Technology (where he heads the Center for Cancer Research) and Scott W. Lowe of Cold Spring Harbor Laboratory have demonstrated, in two separate studies using two markedly different approaches, that advanced cancers still need this tumor-suppressor gene to lie dormant in order to survive.
"We now know that not only do cancer cells remain highly sensitive to p53 activity throughout their development but also that p53 can orchestrate the elimination of tumors in some cases," says Jacks. "This [knowledge] represents an enormous therapeutic possibility." His paper, along with Lowe's, appeared in the February 8, 2007, issue of Nature.