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Be it Darth Vader or Valdemort, it takes a superhero gone bad to make a supervillain. Scientists say it looks like this is also true for cancer. As this ScienCentral News video explains, learning how a small number of good cells went bad may be the key to defeating the disease.
Getting to the Root of Cancer
When a patient is diagnosed with cancer, part of the fear comes from how tenacious cancer can be. "Did they get it all?" many patients ask after cancer treatment, worried about cancer relapse. Cancer researcher Michael Clarke says only a special class of rare cells has the fearsome spreading powers of cancer.
"They are very long-lived," he says. "They can divide an immense number of times and they also, in many cases, have the ability to migrate."
Clarke is talking about stem cells, which normally maintain and replenish our body's cells. He and his colleagues at Stanford University's Institute for Stem Cell Biology and Regenerative Medicine are convinced that cancer is a case of good stem cells gone bad. Irv Weissman, the Institute's director, explains, "that's the only cell that perpetually self-renews -- makes more of itself."
Michael Clarke
When a stem cell divides, it produces another stem cell, along with a "progenitor" cell that can become more and more specialized. For example, blood-forming stem cells in your bone create a "family tree" of specific cells, from red blood cells that carry oxygen to macrophages that fight infection.
As Clarke wrote in Scientific American magazine, environmental or genetic factors can make that process go haywire. "You can think of the mutations that lead to cancer as bad decisions and all of these bad decisions accumulate," he says. "These cells now essentially become Darth Vader ... They were formerly good and absolutely required for our existence, and because of these bad decisions, these genetic mutations that lead to cancer they now become evil. And they are the cells that kill us."
Weissman has studied this pathway in detail in leukemia, in which cancer stem cells were first discovered in 1994. Since then, cancer stem cells have also been found in breast cancer, brain cancers, and prostate cancer. "And in addition to the published cancers, I know of four other types of cancer where the stem cell population has been identified," Clarke says.
Cancer stem cells
Using a sophisticated instrument called a flow cytometer that sorts out stem cells from tissue samples, the researchers can also isolate cancer stem cells from tumors. Then they can test the cells' ability to form new tumors.
"What we found was as few as 100 of the cancer stem cells could easily re-form a tumor whereas tens of thousands of the other cancer cells were totally unable to form a new tumor," says Clarke. "So what this told us was that just because a cell looks like a cancer cell and is a cancer cell, not all of these cells are able to re-form a tumor."
Weissman says isolating these cancer culprits in the lab could reveal how to stop them in the body. "So what we want to do is take advantage of understanding of that pathway to the cancer, to attack the cancer in the patient."
He's applying his research on normal brain stem cells to about the nastiest cancer there is -- glioblastoma multiforme. "It should have been called a brain cancer you can't cure," Weissman says. "If you stain a mouse brain into which you injected the human glioblastoma cancer stem cells, they spread from the place you put them at the beginning to all the predicted sites where norm stem cells go. That means by the time the patient knows that he or she has that disease, the cancer's spread throughout the brain."
Irv Weissman
"Now by knowing how the normal stem cells inhabit the brain and move and replenish the brain and repair injury, we get clues as to the genes that the cancer stem cells use to move and spread and invade in the brain."
The researchers say that will mean future cancer treatments might not need to eliminate every last cancer cell -- just the ringleaders. Clarke says there is already some strong clinical evidence that supports this. He says it was testicular cancer -- the cancer that Lance Armstrong had -- "that got me thinking solid tumors contained a stem cell population."
In patients like Armstrong, "if there are no early or immature cells or stem cell-like cells left in a residual tumor after treatment, the major of those patients are indeed cured," he explains. "Whereas if the therapy doesn't eliminate all those early cells -- even if it causes the tumors to shrink a large amount, 90 percent, 99 percent shrinkage of the tumor -- if there are residual early cells left in those tumors those patients invariably relapse."
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