Study finds way to prevent cancer recurrence

March 2, 2010, 1:01 a.m.

Researchers at the Stanford School of Medicine have discovered a new way to prevent the recurrence of a deadly form of brain cancer called glioblastoma. The breakthrough research, conducted on mice, could have a significant impact on how cancer is treated in humans.

Past research has shown that radiation treatment can be effective on glioblastoma tumors in the short run, but the cancer nearly always recurs, typically resulting in death within a few months. Very few people with this type of brain cancer live for more than two years after diagnosis.

In a study published online in the Journal of Clinical Investigation, Stanford medical researchers found that irradiated tumors (tumors subjected to radiation therapy) use a little-known, secondary pathway to receive the oxygen and nutrients that make growth possible. Researchers found that by blocking these pathways, they could drastically reduce rates of cancer recurrence.

“Under normal circumstances, this pathway is not important for growth of most tumors,” said Martin Brown, a professor of radiation oncology and senior author of the paper, in a report by the School of Medicine. “What we hadn’t realized until recently is that radiation meant to kill the cancer cells also destroys the existing blood vessels that nourish the tumor. As a result, it has to rely on a backup blood delivery pathway.”

While scientists focused on glioblastoma in their research, many other types of tumors use similar mechanisms to evade radiotherapy, suggesting that this research could be broadly applicable to cancer treatment.

Brown and his colleagues used a molecule called AMD3100 to block the secondary growth process. This molecule is already approved for other uses in humans, so it is possible that clinical trials to test the molecule in human patients could take place soon.

However, researchers caution that routine clinical use of this treatment on humans is probably still years away, since there is a demanding, multi-phase testing process that must be carried out before FDA approval can be obtained.

According to Brown, the inspiration for this research project has been years in the making.

“I was looking at some data published by a Harvard lab in 1993 that showed that the sensitivity of tumors to irradiation did not depend on the sensitivity of the tumor blood vessels,” Brown said in an interview with The Daily. “It seemed to me that there must be circulating cells that could reconstitute the tumor blood vessels after irradiation. I thought, ‘if we could prevent these cells coming from the bone marrow [then] we could stop tumors recurring after irradiation.’”

Though much research and testing remains to be done, this discovery has potentially powerful implications for the future of cancer treatment in humans.

“Changing the treatment of solid tumors, which make up 90 percent of all cancers, by irradiation is clearly a likely possible consequence of this research,” Brown said.

In addition to Brown, the study’s contributors are research associate Mitomu Kioi, the paper’s first author, and neurosurgery professor Griffith Harsh, a co-author. Brown and Harsh are members of Stanford’s Cancer Center.

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