Studies find new weaknesses in cancer

WASHINGTON Thu May 28, 2009 2:42pm EDT

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WASHINGTON (Reuters) - Researchers using a new gene-scanning method have found a potential way to fight cancer by silencing genes that tumors need to stay alive.

They found a previously unknown gene that keeps tumor cells from killing themselves but that does not appear to be needed by normal, healthy cells. A second team found another new genetic process that also appears to be unique to tumors.

Both discoveries relate to a gene mutation involved in as many as 30 percent of cancers, the researchers reported in two studies in the journal Cell -- an attractive target for a potentially useful and profitable drug some day.

The studies also point to a quick and effective new way to look for ways to fight cancer, using RNA interference or RNAi, itself a hot area in biotechnology.

Both teams of researchers focused on a known cancer-causing gene called KRAS. Mutations in KRAS are involved in 30 percent of cancers including leukemia, pancreatic and lung cancers. But so-called targeted cancer drugs do not work well against these tumors.

"It's been a real frustration," said Gary Gilliland of Harvard Medical School, who led one of the studies. "We know the mutation but we haven't been able to do a thing about it."

One important field of cancer therapy has been angiogenesis inhibition -- stopping tumors from building blood vessels to feed themselves. Gilliland's team and another group led by Stephen Elledge of Harvard and the Howard Hughes Medical Institute looked for other things tumor cells need.

"Cancer cells aren't super cells," Elledge said in a statement. "They are very sick cells that have needed to make a lot of compromises."

To find these compromises Elledge and Gilliland, who now works at Merck Research Laboratories, used high-throughput RNAi. The employed small stretches of genetic material called RNA to slow down genes systematically.

"This strategy allows us to ask what the best targets are, with no preconceived notions," Elledge said.

Scanning the entire human genome, Elledge's team found some genes that KRAS cancers depend on to survive. One group they found are on what is known as the PLK1 pathway.

Gilliland's team focused on a type of gene known as a kinase, already targeted successfully by cancer drugs. They found one called STK33 that appears to keep cancer cells from self-destructing when they are supposed to.

"The beauty of the strategy is that it would take only 50 to 70 percent knockdown of STK33 to kill a cancer cell," Gilliland said. "It relies on a unique frailty of the cancer cell that normal cells don't have."

The work is highly experimental and will take years to translate into human research. But, Gilliland said, "We were looking at genes that we thought we could target easily with drugs."

(Editing by Bill Trott)

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