Turning off the "master switch" for cancer

Researchers at the British Columbia Cancer Agency (BCCA) have made a major breakthrough with the discovery of a "master switch" that can turn off tumour growth in several common types of cancer. The findings could result in promising new treatments for cancer (Proc Natl Acad Sci USA 2000;97[7]:3207-12).

Dr. Shoukat Dedhar, a senior scientist at the agency, and his colleagues at Vancouver's Kinetek Pharmaceuticals have found a connection between a key tumour suppressor gene called PTEN and the integrin-linked kinase (ILK) protein, which plays a major role in the growth of cancer cells.

ILK prevents tumour cell death, allowing tumours to grow (the "on" switch). In normal cells, the PTEN gene controls ILK (providing the "off" switch). However, PTEN is mutated or absent in 60% of all solid types of cancer. Dedhar's research indicates that ILK is hyperactive in many of these types of cancer, including prostate, breast, brain, lung and colon cancer. Using human lung, prostate and colon cancer cells, Dedhar and Kinetek's Dr. Jasbinder Sanghera have developed promising ILK-inhibiting compounds that block the formation of new blood vessels and prevent the spread of tumour cells. Experimenting with mice in which human tumours had been transplanted, as well as in human prostate cancer cells, the researchers found that ILK inhibitors induced cell death in prostate cancer cells and reduced the spread of the tumours. FIGURE

Figure. Diagram shows how ILK functions as the "on" switch within cells, inducing cell responses seen in cancer, whereas the PTEN gene functions as the "off" switch, preventing this process.

"This is both amazing and exhilarating," said Dedhar. "Inhibiting ILK may not only result in inhibiting growth of the primary tumour but may also lead to reducing the subsequent spread of the tumour cells. And unlike standard chemotherapy agents, these inhibitors do not appear to kill or harm healthy cells. We now know that if we inhibit ILK, we might be able to treat tumours in novel ways. We envisage that these anti-ILK compounds may be used with low-dose conventional chemotherapy."

Dr. Victor Ling, vice-president of research at the BCCA, commented: "This is exciting news for cancer patients everywhere. A targeted therapy with fewer side effects will mean better results for those living with cancer."

Phase 1 clinical trials of ILK inhibitors are expected to start within 2 years.