Researchers at the BC Cancer Agency have discovered a new way to halt the growth of some cancers by shutting down their blood supply.

A new study, appearing tomorrow in the journal Cancer Cell, suggests a method to deprive tumours of important blood vessels. Most solid tumours rely on a blood supply to survive. So destroying existing blood vessels to a tumour, and preventing the growth of new vessels - known as anti-angiogenesis – has been the focus of intense investigation. However, to date, with the exception of Avastin, most anti-angiogenesis drugs have failed in clinical trials.

The team, led by BC Cancer Agency senior scientist Dr. Shoukat Dedhar and MD/PhD student Clara Tan, has now identified a new target for anti-angiogenic therapy. They have found that by inhibiting the function of a protein called Integrin-Linked Kinase (ILK), they could prevent the growth of blood vessels in human tumours transplanted in mice and significantly slow down the growth of the tumours.

ILK plays an interesting dual role in the support of tumour growth. Dr. Dedhar and his colleagues have found that overactive ILK in tumour cells promotes the secretion of a factor called vascular endothelial growth factor (VEGF) which is required for the formation of new blood vessels. Thus, by inhibiting ILK function, VEGF production by the tumour cells is blocked. What makes this study even more exciting is that it shows that the function of ILK is also essential in endothelial cells, which are the building blocks of blood vessels, and are stimulated to grow and form new blood vessels in response to VEGF. The team found that inhibiting ILK function in endothelial cells prevented the cells from growing and coming together to form blood vessels in response to VEGF.

Knocking out ILK function, therefore, may not only stop the creation of blood vessels that feed a tumour, but may also halt the growth of the tumour itself as the cells cease to reproduce. And by eliminating the blood vessels, not only does the tumour stop growing, but it also is unable to spread throughout the body as individual cancer cells split from the original site.

Researchers at the BC Cancer Agency and the Prostate Centre at VGH have already completed successful tests to knock out ILK function in mouse models of human prostate tumour growth using a compound developed in partnership with a local pharmaceutical company.

Interestingly the studies suggest that the compound is effective when taken orally. Once the growth of the tumour is halted, chemotherapy or radiation therapy can then be used to destroy the residual tumour tissue.

Dr. Dedhar expects that within a year, the BC Cancer Agency could begin clinical trials in breast and prostate cancer patients.

The research, says Dr. Dedhar, is a good example of the BC Cancer Agency's translational research program, aimed at taking new discoveries from the lab bench to the patient as quickly as possible.

"Here we have a scientific advance with very clear clinical implications," he says.

While the research has focused on prostate cancers, Dr. Dedhar believes that it will have applications to most solid cancers, such as colon cancer, breast cancer, pancreatic cancer and brain cancers. This new information about ILK is particularly exciting because the gene was first discovered in Dr. Dedhar's lab in 1996.

The BC Cancer Agency, a part of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Research Centre conducts research into the causes and cures for cancer.

Nicole Adams
Public Relations Officer
BC Cancer Agency
Ph. (604) 877.6272
Pager (604) 641.5167