An Indian origin researcher at The University of Texas M. D. Anderson
Cancer Center has identified the mechanism whereby a protein that fuels ovarian cancer can be shut down.
'The protein interleukin-8 (IL-8) is a potential therapeutic target
in ovarian cancer,' said Dr. Anil Sood, a professor in the M. D. Anderson Departments of Gynecologic Oncology and Cancer Biology.
Writing about the research team's findings in a paper, published in the
Journal of the National Cancer Institute, Dr. Sood said that high IL-8
expression in tumours is associated with advanced tumour stage, and earlier death for ovarian cancer patients.
He revealed that experiments conducted on a mouse model had revealed
that short interfering RNA (siRNA) could cut IL-8 expression, and reduce tumour 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,' Dr. Sood said.
Pointing out that IL-8 is over-expressed in many types of cancer, Dr. Sood added: 'In the long run, this research will have applications in other cancers as well.'
During the study, the researchers tested a specific siRNA against two
lines of ovarian cancer in a mouse model. They packaged siRNA that stymies IL-8 into a small ball of fat known as a liposome, a combination they developed because siRNA is hard to deliver to tumours.
The researchers found that tumours shrank by a median of 32 per cent and
52 per cent in the two cancer lines among mice that received injections of the IL-8 siRNA liposome compared to those receiving control siRNA or empty liposomes.
Animals receiving both the IL-8 siRNA and the taxane-based chemotherapy
drug docetaxel had median tumour weight reduction of 90 per cent and 98 per cent in the two cell lines, said the researchers.
They further said that mice with control siRNA and docetaxel saw
reductions of 67 and 84 per cent.
Upon testing the approach in mice with an ovarian cancer cell line known
to be resistant to taxane-based drugs, the researchers observed that IL-8 siRNA alone reduced the size of these tumours by 47 per cent, and by 77 per cent when combined with docetaxel.
The researchers said that the finding suggested that the combination
re-sensitised a resistant tumour to taxanes.
According to them, the IL-8 siRNA was also found to reduce blood vessel
density by 34 per cent and 39 per cent in two cancer lines.
'These are encouraging results. We want to move one of our siRNA agents into the clinic to test its potential for therapy, and then in the longer term, we'll consider moving additional siRNA agents into the clinical arena,' Sood said.