A protein developed by scientists at Oregon Health & Science University blocks the growth of glioblastoma, an aggressive and deadly brain tumour, in laboratory rats, according to a recent study.

Herstatin inhibits the activation of a family of enzymes responsible for signalling inside tumour cells that tells the cells to proliferate and display other malignant properties, said Gail Clinton, professor of biochemistry and molecular biology in the OHSU School of Medicine who co-authored the study.

Over-expression of the epidermal growth factor (EGF) receptors results in a cascade of signals in the glioblastoma cells that drive their growth. But herstatin, a naturally occurring product, blocks growth of the cells by binding to EGF receptors and turning signalling off.

Clinton said human clinical trials for herstatin could begin as early as next year. In fact, the technology is part of a patent portfolio that OHSU has licensed exclusively to San Francisco-based pharmaceutical company Receptor BioLogix Inc., which is developing herstatin as a cancer therapeutic for a variety of cancer types under the name Dimercept.

According to the nonprofit Central Brain Tumour Registry of the United States, glioblastomas account for the majority - 52 per cent - of all gliomas, which are tumours that arise from glial cells and include astrocytomas, oligodendrocytomas, ependymomas, mixed gliomas, malignant gliomas NOS (nitric oxide synthase), and neuroepithelial tumours. Glioblastomas make up 23 per cent of all brain and central nervous system tumours.

Scientists used herstatin to treat human glioblastoma cells grown in culture and implanted in rats. "We saw a few tumor cells at the injection site, but they never proliferated," Clinton said.

Herstatin was not effective on a mutant form of the EGF receptor, called EGF receptor delta. The mutant receptor causes even more aggressive tumour growth in a subset of glioma.

"We found our inhibitor targets the full-length EGF receptor, but not the mutant EGF receptor," Clinton said adding, "So a patient with a glioma generated by the mutant EGF receptor would not be expected to respond to herstatin."

She added, "This inhibitor we have is a naturally occurring one, and it's possible that the mutant EGF receptor may have developed to confer resistance to the class of inhibitors that blocks the extracellular domain" on the glioblastoma cells. About a third of all glioblastomas derive from the mutant receptor, Neuwelt said.

Although herstatin is not effective against the mutant EGF receptor, the study's results demonstrate highly selective molecules can be developed to target pathogen cells, reducing the chance that other complications will crop up when treating diseases.

"It gives new information about which tumours to target, what molecular profile is important to look at up front, but it also tells us that herstatin is a specific inhibitor," Clinton noted. "This is another step in proving it doesn't kill all cells, and the more specific and tailored it is to a particular molecular profile, the less likely you're going to have a lot of side effects," she added.