Interleukin (IL)-8 offers a potential therapeutic target in ovarian cancer,

Interleukin (IL)-8 offers a potential therapeutic target in ovarian cancer,

* w w w .medscape . com /viewarticle/570776
Interleukin-8 Offers New Therapeutic Target in Ovarian Cancer

February 27, 2008 — Interleukin (IL)-8 offers a potential therapeutic
target in ovarian cancer, and might also have potential in other cancers,
say researchers from the University of Texas MD Anderson Cancer Center in
Houston. They have already developed products comprised of liposomes and
small interfering RNA (siRNA) that can block IL-8, and these have shown
activity against ovarian cancer lines in 2 mouse models. The team is hopes
to test a similar product in humans within a year.

The research is reported in the February 26 issue of the Journal of the
National Cancer Institute and highlighted in a press release from the
university. Senior author Anil Sood, MD, said that the paper presents a
"comprehensive analysis — with human data, animal data, and lab
experiments to highlight the molecular mechanisms involved." IL-8 is
overexpressed in many cancer types, and has previously been shown to
promote tumor growth, angiogenesis, and metastases. "In the long run, this
research will have applications in other cancers as well," he commented.

Dr. Sood and colleagues showed that cytokine is associated with more
severe cases of ovarian cancer. By analyzing tumor tissue from 102
patients, they found that 43 patients had tumors with high levels of IL-8.
All of these tumors were high grade, and 42 of 43 were advanced, either
stage 3 or 4; the median survival of these patients was 1.62 years. In
contrast, the remaining 59 tumors had a low expression of IL-8; of these,
6 of 59 tumors were low grade and 10 of 59 were early stage. The median
survival of these patients was 3.79 years.

The team developed a siRNA product that specifically blocks the
transcription of the gene that codes for IL-8, thereby blocking production
of this protein, and encases it in a liposome delivery system. In mouse
studies, this product showed activity against 2 ovarian cancer cell lines,
both when used alone and when used in combination with docetaxel. In
addition, the mouse studies revealed that the product was decreasing tumor
growth through anti-angiogenic mechanisms — the treated tumors showed a
lower microvessel density, the researchers report. This product was
"highly effective in our preclinical studies and may merit clinical
development," they write.

However, they also caution that the cell lines used to create the mouse
models might not accurately reflect the heterogeneity seen in human
tumors.

Dr. Sood and colleagues have also developed similar liposomal siRNA
products that block the oncoproteins Fak and EphA2. Of these, EphA2 is
closest to clinical trial; toxicology studies are nearly completed.

The researchers have disclosed no relevant financial relationships. These
studies were funded in part by grants from the National Cancer Institute.

J Natl Cancer Inst. 2008;100:359-372.
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EphA2 is a transmembrane receptor tyrosine kinase that is overexpressed in
many carcinomas. Specific targeting of EphA2 with monoclonal antibodies
American Journal of Pathology. 2003;163:2271-2276