Scientists are developing a "smart bomb" that can deliver anti-cancer drugs directly to tumors without damaging nearby tissues.
Although they will have to prove their efforts will not cause more harm than good before the first clinical trials can get under way, the researchers believe they will be able to deliver powerful drugs precisely to inoperable targets throughout the brain.
The first trials are at least two years or three years away, and many profound questions must be answered before they can begin, so this isn't likely to show up in clinics for a number of years, if ever.
So far, the process has been tested only in rodents, and it involves a procedure that is likely to cause much concern among regulatory officials -- injection of stem cells into the brain from a source other than the patient.
"It's a very novel, promising therapy," said the lead researcher, Karen Aboody of the City of Hope Cancer Center in Duarte, Calif., one of the leading cancer research and treatment facilities in the world.
Aboody, who began her work during a 12-year stint at Harvard University, believes she and her six-person team have found a way to precisely target even tiny tumors scattered throughout the brain without the devastating side effects of chemotherapy, which normally kills healthy cells along with cancerous cells.
They also have figured out how to get over a very difficult hurdle. If delivered to a brain tumor, chemotherapy drugs can work wonders, but they are blocked from entering the brain by one of the brain's defense mechanisms, called the blood-brain barrier.
The researchers have gotten past the barrier by developing a way to turn a benign drug into a chemotherapeutic agent after it gets to the tumor.
"We're taking advantage of a natural property," Aboody said.
Aboody, with collaborators at Tufts-New England Medical Center and Brigham and Women's Hospital in Boston, have turned stem cells -- those mysterious cells that can morph into just about any cell they want to be -- into drug delivery vehicles that naturally home in on tumors. The researchers described their work in the April issue of the journal Neuro-Oncology.
Aboody began her work while running preclinical therapy trials for brain tumors at Harvard. Most of the therapies failed, she says, because a drug doesn't always go where you want it to go. Even if delivered to the target, the drugs didn't "move toward invading tumor cells," she said.
That was a particularly troubling problem because many of the patients studied by Aboody were suffering from cancer that metastasizes, or spreads, to the brain from other organs, like the lungs.
Instead of having one large tumor that might be removable by a surgeon, these patients had many smaller tumors so widely spread throughout the brain that nothing could be done for them.
While working with rodents, Aboody and her colleagues made an amazing discovery. When injected into the brain of a rodent that had been engineered to have brain cancer, neural stem cells zoomed in on the tumors like an arrow seeking a target.
No one knew then why the cells were attracted to tumors, but years of research have finally produced at least a partial answer.
Cancerous cells try to produce new blood vessels to feed themselves, and the stem cells seem to be attracted to that, she says. Cancerous cells are also damaged cells, and as part of the body's repair system, stem cells are naturally attracted to damaged areas as well.
Aboody found that she could even introduce stem cells to the opposite side of the brain from the tumors and that the cells would maneuver their way quickly to the cancer.
Fascinating discovery, but what do you do with it? The researchers found that they could engineer the stem cells to produce an enzyme once they reached the tumor. Then researchers introduced a benign drug, called 5-FC, that could get past the blood-brain barrier, and injected it into the rodents.
"When it sees the enzyme that the stem cells are making, it converts to a chemotherapeutic agent [5-FU] at that site," Aboody said. The drug attacks the cancerous cells, and there is no sign of damage to adjacent tissue -- a very important finding.
So the researchers had their delivery system, and a drug that could be turned into a cancer killer at just the right moment, but there was a problem. What if, once inside a human brain, the stem cells decided not to cooperate and turned into something totally undesired by the scientists?
"Neural stem cells change over time," Aboody said. "So you don't know that what you had a month ago is the same thing that you have now."
Fortunately, scientists at the University of British Columbia were working on a similar problem and had engineered a line of stem cells that had been robbed of their ability to morph into a different kind of cell.
Aboody started using those cells in her work and found that not only did they remain unchanged, they soon died if they couldn't find cancerous cells.
So she believes she has found her delivery vehicle, which can be produced "by the billions" in a lab at the City of Hope. There are still some enormous questions that have to be answered.
One of the hottest areas of cancer research these days concerns the discovery that some stem cells produce cancer, and it may be possible to block that, thus eliminating some types of cancer.
That's good news for other researchers, but a problem for Aboody. She will have to prove to the Food and Drug Administration that the stem cells she uses are not cancer-causing stem cells.
If she can answer that, as well as dozens of other questions that are expected to be raised, she may get approval in a couple of years to begin clinical trials involving a handful of people who desperately need help that is not now available.
It is literally a life and death issue that Aboody knows firsthand. Five years ago, her sister-in-law died of breast cancer that had spread to her brain, becoming inoperable.