• 10/3/2006
  • Houston, TX
  • staff
  • MD Anderson Cancer Center (www.cancerwise.org)

Genetic Fragments Turn Off Cancer Growth Switch

In experiments with mice, researchers have determined how to embed molecular “off” switches into fatty spheres and send these tiny blobs down the bloodstream into ovarian cancer cells to stop tumor growth.

Significance of results

The therapy reduced the size of ovarian tumors by up to 98% in mice, and it was well tolerated, say senior authors Anil Sood, M.D., associate professor in M. D. Anderson’s Department of Gynecologic Oncology and Department of Cancer Biology, and Gabriel Lopez-Berestein, M.D., professor in the Department of Experimental Therapeutics.

“We hope to develop this approach for clinical use in the future,” Sood says.

The study, reported in the Aug. 15 issue of the scientific journal Clinical Cancer Research, uses the freshest technologies developed in cancer research laboratories. These tools include spheres of fat known as nanoparticles and bits of RNA that can target genes involved in cancer growth and “silence” them.

Background

RNA is produced from activated DNA (the master genetic code) and serves as a template for producing proteins, the workhorses of cells. But researchers recently discovered that special fragments of RNA can reverse the DNA-RNA-protein process and turn off selected genes so that they cannot order the production of dangerous proteins.

These are called “small interfering” RNA, or siRNA. This finding was followed by the discovery that siRNA can target cancer-promoting genes. Now researchers can artificially create the siRNA they want.

Scientists have shown that tumors will shrink when siRNA is inserted directly into them in a laboratory, but they also have said that such methods have not been practical for human patients.

Research methods

The current study shows how the M. D. Anderson researchers solved the problem, and how it worked in mice using siRNA, which targets a protein known as FAK.

FAK helps ovarian cancer cells survive and spread. The siRNA was rolled into a liposome – a ball of fat so small that its dimensions are measured in nanometers (billionths of a meter). Because of their tiny size, these liposomes have no problem traveling through the blood supply into cells that make up tumors, the researchers say.

To test how well it worked, mice that were implanted with human ovarian tumors were given injections of the therapy for three to five weeks.

Primary results

Their tumors experienced a 44% to 72% reduction in weight, Sood says. Adding chemotherapy to the treatment boosted tumor weight reduction to the 94% to 98% range.

What’s next?

The next step for the FAK siRNA liposome is testing it for toxicity prior to studies in human patients, Sood says. The researchers suggest that this approach could provide potential benefit to other cancers because over-production of FAK occurs in colon, breast, thyroid, and head and neck cancers.