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| From OncoLog,
April 2008, Vol. 53, No. 4 |
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Cancer-Promoting Protein in Ovarian Cancer May Be Stopped with RNA Liposome
The protein interleukin-8 (IL-8) appears to promote the growth of ovarian cancer, but its production can be stopped by a specific bit of RNA, a research team led by scientists at M. D. Anderson reported recently in the Journal of the National Cancer Institute.
To examine IL-8’s role in ovarian cancer, the team analyzed tumors from 102 patients diagnosed and treated between 1988 and 2006 at M. D. Anderson and the University of Iowa. Of these patients, 43 had tumors with high levels of IL-8. The median overall survival of patients with high IL-8 expression was 1.62 years, compared with 3.79 years for those with low expression. All 43 tumors with high expression of IL-8 were of high grade, and 42 were stage III or IV tumors.
The researchers then identified a specific chain of short interfering RNA (siRNA) that stopped production of IL-8 in laboratory testing. They tested this siRNA against two lines of ovarian cancer in mice by inserting it into a liposome, which served as a vehicle to the tumors.
Among mice receiving injections of the IL-8 siRNA liposome, tumors from the two lines shrank by a median of 32% and 52%. Median tumor weight shrank by 90% and 98% in mice receiving both IL-8 siRNA and the taxane-based chemotherapy drug docetaxel. Mice receiving control siRNA plus docetaxel had reductions in tumor weight of 67% and 84%. IL-8 siRNA alone reduced blood vessel density in tumors by 34% and 39%.
In mice with an ovarian cancer known to be resistant to taxane-based drugs, IL-8 siRNA alone reduced tumor size by 47%. When the IL-8 therapy was combined with docetaxel in these mice, tumor size decreased by 77%, suggesting that the combination re-sensitizes a resistant tumor to taxanes.
IL-8 is overexpressed in many types of cancer and has been shown to promote tumor growth, angiogenesis, and metastasis. “In the long run, this research will have applications in other cancers as well,” said Anil Sood, M.D., a professor in the M. D. Anderson Departments of Gynecologic Oncology and Cancer Biology and senior author of the research. The IL-8 siRNA liposome is the third developed by M. D. Anderson researchers as a way to potentially deliver inhibitors to cancer-promoting proteins.
Along with Dr. Sood, the development of these liposome delivery systems is being led by Gabriel Lopez-Berestein, M.D., a professor in the Department of Experimental Therapeutics. A phase I clinical trial of a liposome containing the oncoprotein EphA2 could begin within a year.
For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.
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