Novel anti-cancer strategy targets ‘intercept points’ for cancer cells

Cancer CellWashington, Jan 4 : Scientists at the Emory University have made an advancement in the fight against cancer, by developing an anti-tumour compound called SF1126, which represents a unique strategy of targeting one of the most important "intercept points" for cancer cells.

The strategy was first used in human patients with solid tumors in 2007 and was shown to be active against prostate, breast, renal, multiple myeloma, neuroblastoma, glioblastoma and rhabdomyosarcoma.

The study was led by Donald L. Durden, MD, PhD, professor of pediatrics at Emory University School of Medicine and the Emory Winship Cancer Institute and scientific director of the Aflac Cancer Center and Blood Disorders Service at Children's Healthcare of Atlanta.

According to Dr. Durden, the underlying idea behind the intercept point strategy was to stop the transmission of a large number of growth signals in cancer cells at one go.

He also compared a cancer cell to a building with too many of the lights left on.

"Doctors have been trying to treat cancer by turning out the lights in one room at a time, instead of going after the transformer box," he said.

The researchers targeted a class of enzymes called PI-3 kinases, which represent an intercept point and is present in a large amount in almost every cell in the body.

"Nature made these enzymes central in controlling growth, differentiation and survival. But you can't hit only one of them; they're redundant,” said Dr. Durden.

The researchers demonstrated that the chemical inhibitor of all PI-3 kinases, which was modified with a tag directing the SF1126 compound to the blood vessels needed by growing tumors, resulted in stopping the growth of seven types of tumors in mice.

Scientists use PI-3 kinase inhibitors in test-tube experiments every day, however, the enzyme-inhibiting part of SF1126 was never used clinically despite its identification more than a decade ago.

At the end of 2007, doctors in Arizona and Indiana began to test SF1126 in a phase I clinical trial in people with solid tumors. Another phase I trial for multiple myeloma patients will begin at Emory's Winship Cancer Institute and elsewhere in 2008. It is anticipated that SF1126 will enter pediatric cancer trials within one year.

The authors also showed that if a tag called RGD peptide is attached to the compound, it makes the inhibitor dissolve easier and last longer in the body. It also lets molecules on blood vessel walls seize the compound and send it into tumors. When the tumors lack oxygen, they send out signals for new blood vessels.

It was discovered in mice that SF1126 compound prevents tumors from growing new blood vessels by inhibiting part of their response to the lack of oxygen.

SF1126 also sensitizes human tumors in mice to a chemotherapy agent called taxotere.

The study appears in the recent issue of Cancer Research. (ANI)