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December 27, 2005
Killing Cancer Cells-- Finally?
Very positive news:
At first, as scientists grew to appreciate the complexity of cancer genetics, they despaired. "If there are 100 genetic abnormalities, that's 100 things you need to fix to cure cancer," said Dr. Todd Golub, the director of the Cancer Program at the Broad Institute of Harvard and M.I.T. in Cambridge, Mass., and an oncologist at the Dana-Farber Cancer Institute in Boston. "That's a horrifying thought."
Making matters more complicated, scientists discovered that the genetic changes in one patient's tumor were different from those in another patient with the same type of cancer. That led to new questioning. Was every patient going to be a unique case? Would researchers need to discover new drugs for every single patient?
"People said, 'It's hopelessly intractable and too complicated a problem to ever figure out,' " Dr. Golub recalled.
But to their own amazement, scientists are now finding that untangling the genetics of cancer is not impossible. In fact, they say, what looked like an impenetrable shield protecting cancer cells turns out to be flimsy. And those seemingly impervious cancer cells, Dr. Golub said, "are very much poised to die."
Despite the thousands of possible genetic abberrations and reconfigurations, scientists have discovered all cancer develops along ten pathways, and that shutting those pathways down can eliminate the disease.
Cells typically repair genetic defects....
But one of the first things a cell does when it starts down a road to cancer is to disable repair mechanisms. In fact, BRCA1 and 2, the gene mutations that predispose people to breast and ovarian cancer, as well as some other inherited cancer genes, disable these repair systems.
Once the mutations start, there is "a kind of snowball effect, like a chain reaction," Dr. Vogelstein said.
With the first mutations, cells multiply, producing clusters of cells with genetic changes. As some randomly acquire additional mutations, they grow even more.
In the end, all those altered genes may end up being the downfall of cancer cells, researchers say.
"Cancer cells have many Achilles' heels," Dr. Golub says. "It may take a couple of dozen mutations to cause a cancer, all of which are required for the maintenance and survival of the cancer cell."
And undoing just one of those mutations -- repairing one key mutation through genetic-drug therapy -- would kill the cancer and stop it from replicating further.
So cool.