Anti-Cancer 'Smart Bomb' Homes in on Deadly Tumors

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Dec. 21, 2006 — Scientists have made astonishing progress in developing a "smart bomb" that can deliver powerful cancer-fighting drugs directly to tumors scattered throughout the body, thus minimizing damage to healthy tissue and easing the wretched side effects of chemotherapy.

The research builds on earlier work that showed that an engineered version of the stem cell could home in on a brain tumor and deliver drugs directly to the target area. But this is the first time that research has shown that the same process might be used to attack cancer that has metastasized throughout the body.

So far the research has been limited to mice, but scientists are hopeful that clinical trials involving humans with advanced cancer can begin reasonably soon, possibly in less than a couple of years.

Karen Aboody, of the City of Hope Cancer Center in Duarate, Calif., said she is very encouraged by experiments that showed a remarkable recovery by mice inflicted with a human cancer and treated with the new process. She is the lead author of a report published in the current issue of the peer-reviewed journal, PLoS One. A second report is scheduled for publication next month in Cancer Research.

Of course, what works for mice may not work for humans, and the scientists must prove that the treatment does no serious harm before they can proceed to clinical trials that would determine whether it does any good. So there's still a long ways to go, but the results in the animal studies are nothing less than remarkable.

Aboody, who began her line of research during a 12-year stint at Harvard University, teamed up with experts at several other institutions, most notably Mary Danks, of St. Jude Children's Research Hospital in Memphis, Tenn., for her latest round of experiments. The work is sponsored by the National Cancer Institute and several research foundations.

It's a perfect match in that St. Jude has been pioneering research into powerful new cancer drugs and City of Hope has been developing a unique delivery system using specially engineered stem cells. The research involves a type of cancer called neuroblastoma, which accounts for up to 10 percent of all childhood solid tumors (excluding blood cancers like leukemia) worldwide. It's a common tumor among children, and most patients with metastatic neuroblastoma die of their disease. Neuroblastoma develops from nerve cells in several areas of the body and is the most common cancer in babies.

There is much interest in a drug called SN-38 that is extremely effective and a potent tool in the fight against cancer, but is hard to administer.

"You can't just pump that through a kid's system," Aboody said. "It's too toxic."

If it could be delivered directly to the tumors, no matter where they are in the child's body, it would do much to alleviate the often fatal impact of neuroblastoma. And that's where the latest research comes in.

Stem cells have shown a remarkable ability to home in on cancerous tissue, possibly because the tissue is damaged, and maybe because the cancerous cells try to produce new blood vessels. Whatever the cause, Aboody recognized that the attraction of stem cells to tumors offered the possibility of building a very precise delivery system.

Using a line of stem cells developed at the University of British Columbia Hospital in Vancouver that can be easily reproduced in the lab, Aboody and her colleagues engineered the cells to carry an enzyme that could enrich the standard chemotherapy drug, CPT-11.

"CPT-11 is the drug that's used to treat kids today," Aboody said. "It goes throughout the body and only a very small percent of it reaches the tumors."

But the researchers found that when CPT-11 encounters an enzyme secreted by the stem cells, it turns into SN-38.

"That's a thousand times more effective than CPT-11," Aboody said.

But it kills everything it encounters.

So the researchers treated mice that had been inflicted with metastasized tumors three different ways. One group of mice was given no treatment at all. They all died by day 75.

The second group received only CPT-11.

"At first they responded, but then they stopped," Aboody said. "They survived longer, but by day 175 only about 50 percent were alive."

The rest of the mice were given both the CPT-11 and the stem cells engineered to convert it to SN-38 at the site of the tumor.

They were all alive at day 175.

The scientists took another look at the animals a year into the study. Only 30 percent of those given just CPT-11 were still alive. But 90 percent of those treated with stem cells and CPT-11 were still alive.

"So that's a year, on a two-and-a-half-year lifespan," Aboody noted.

However, there is some concern among researchers over the end result of introducing foreign stem cells into any human. These remarkable cells can morph into any type of cell tissue, and what would happen if the cells introduced in the fight against cancer turned eventually into something quite harmful?

That concern alone could hold up human trials, but preliminary findings from Aboody and her colleagues indicate that the cells don't hang around after knocking out the cancer.

"When we looked at the organs of the mice that survived a whole year we didn't see any sign of tumors or stem cells," she said.

She theorized that the stem cells may fall victim to their own mission.

"They are giving off this enzyme and the drug is surrounding it, and it's killing all the tumor cells, and it's a very toxic environment," she said. "So it's likely the stem cells are also eliminated."

That would be convenient, to say the least. After they've completed their mission, they're destroyed by the toxicity they helped deliver.

A lot more research will have to be finished before that's known for sure, but Aboody has already set her sights on another target.

She wants to show that the same system can be used to target such common cancers as lung, prostate and breast.

The latter is of special concern to her — she lost her sister—in-law to breast cancer five years ago, and her research is dedicated to her memory.

Commentary by Lee Dye

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