New drug 200 times more active against tumour cells

A new anti-cancer agent, developed by a team of 24 researchers in the US, is nearly 200 times more active in killing tumour cells than similar drugs used in recent clinical trials.

A new anti-cancer agent, developed by a team of 24 researchers in the US, is nearly 200 times more active in killing tumour cells than similar drugs used in recent clinical trials.

The new agent belongs to a class of drugs called bisphosphonates, originally developed to treat osteoporosis and other bone diseases, but recently found to also have potent anti-cancer and immunity-boosting properties.

Drug developers have tried for years to design drugs to inhibit cell survival pathways in tumour cells, focusing on a protein called Ras. Nearly a third of all human cancers involve a mutation in the Ras gene that causes cell signalling to go awry. These efforts have met with limited success.

But bisphosphonates act on other enzymes, called FPPS and GGPPS, which are upstream of Ras in the cell survival pathway. Inhibiting these enzymes appears to be a more effective strategy for killing cancer cells.

When used in combination with hormone therapy in a recent clinical trial, bisphosphonate drug zoledronate significantly reduced the recurrence of breast cancer in premenopausal women. Similar results were reported previously for hormone-refractory prostate cancer.

However, zoledronate quickly binds to bone, reducing its efficacy in other tissues.

"We're trying to develop bisphosphonates that will be very active but won't bind to the bone, because if they bind to the bone they are not going to go to breast, lung or other tissues," said University of Illinois chemistry professor Eric Oldfield, who led the new study.

The study appeared this week in the Journal of the American Chemical Society.