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Fatty spheres loaded with siRNA shrink ovarian cancer tumors in preclinical trial

(HOUSTON) -- A molecular "off" switch packaged in a tiny sphere penetrates deeply into ovarian cancer tumor cells, stifling a troublesome protein and drastically reducing the size of tumors, researchers at The University of Texas M. D. Anderson Cancer Center report in the Aug. 15 edition of Clinical Cancer Research.

The mouse model experiment, featured on the cover of the journal, demonstrates a potent delivery system for short interfering RNA (siRNA) to attack cancer, says senior author Anil Sood, M.D., associate professor in the Departments of Gynecologic Oncology and Cancer Biology at M. D. Anderson.

"Short interfering RNA is a great technology we can use to silence genes, shutting down production of harmful proteins," Sood says. "It works well in the lab, but the question has been how to get it into tumors." Short pieces of RNA don't make it to a tumor without being injected directly, and injection methods used in the lab are not practical for clinical use.

The research team took siRNA that targets a protein that helps ovarian cancer cells survive and spread and rolled it into a liposome -- a lipid ball so small that its dimensions are measured in nanometers (billionths of a meter).

Getting the siRNA inside tumor cells is important, Sood said, because the targeted protein, focal adhesion kinase (FAK), is inside the cell, rather than on the cell surface where most proteins targeted by cancer drugs are found. "Targets like FAK, which are difficult to target with a drug, can be attacked with this liposomal siRNA approach, which penetrates deeply into the tumor," Sood said.

Mice infected with three human ovarian cancer cell lines derived from women with advanced cancer were treated for 3-5 weeks. They received liposomes that contained either the FAK siRNA, a control siRNA, or were empty. Some mice received siRNA liposomes plus the chemotherapy docetaxel.

Mice receiving the FAK-silencing liposome
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Contact: Scott Merville
sdmervil@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
15-Aug-2006


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