Researchers identify protein that fuels ovarian cancer

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A protein that stimulates blood vessel growth worsens ovarian cancer, but its production can be stifled by a tiny bit of RNA wrapped in a fatty nanoparticle, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports in the Journal of the National Cancer Institute.

“The protein interleukin-8 (IL-8) is a potential therapeutic target in ovarian cancer,” said senior author Anil Sood, M.D., professor in the M. D. Anderson Departments of Gynecologic Oncology and Cancer Biology.

The paper demonstrates that high IL-8 expression in tumors is associated with advanced tumor stage and earlier death for ovarian cancer patients. Lab experiments and research in a mouse model show that short interfering RNA (siRNA) can cut IL-8 expression, reducing tumor size by attacking its blood supply.

“This comprehensive analysis – with human data, animal data and lab experiments to highlight the molecular mechanisms involved – helps us develop the new targets needed for a more effective approach against ovarian cancer,” Sood said.

Interleukin-8 is overexpressed in many types of cancer and has previously been shown to promote tumor growth, new blood vessel growth known as angiogenesis, and metastasis, the spread of cancer to other organs. “In the long run, this research will have applications in other cancers as well,” Sood said.

His research focuses on ovarian cancer, for example, while senior co-author Menashe Bar-Eli, Ph.D., professor in M. D. Anderson’s Department of Cancer Biology, examines IL-8’s role in melanoma.

“These are encouraging results. We want to move one of our siRNA agents into the clinic to test its potential for therapy,” Sood said, “and then in the longer term, we’ll consider moving additional siRNA agents into the clinical arena.”

Co-authors with Sood, Bar-Eli and Lopez-Berestein are first author William Merritt, Yvonne G. Lin, Whitney Spannuth, Aparna Kamat, Liz Han, Charles Landen, and Nicholas Jennings, all of M. D. Anderson’s Department of Gynecologic Oncology; Robert Langley and Gabriel Villares, both of M. D. Anderson’s Department of Cancer Biology; Angelina Sanguino, of M. D. Anderson’s Department of Experimental Therapeutics; Mavis Fletcher of the Nebraska Medical Center Department of Pathology and Microbiology; Koen De Geest of the University of Iowa Hospitals and Clinics Department of Obstetrics and Gynecology; and Susan Lutgendorf of the University of Iowa Department of Psychology.

Source: University of Texas M. D. Anderson Cancer Center, USA


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