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New Drug Agent That Kills Multiple Enzymes In Cancer Pathway Developed

by VR Sreeraman on Mar 27 2009 12:17 PM

An international team of researchers have come up with a new anti-cancer agent that is about 200 times more active in killing cancer cells than other drugs used in clinical trials to date.

Led by University of Illinois scientists, the team of 24 researchers have revealed that the new agent belongs to a class of drugs called bisphosphonates.

According to them, such compounds were originally developed to treat osteoporosis and other bone diseases, but were recently found to also have potent anti-cancer and immune boosting properties.

Emphasizing that nearly a third of all human cancers involve a mutation in a gene called Ras, which causes cell signalling to go awry, the researchers highlight the fact that efforts to design potential drugs to prevent such irregularity have met with limited successful.

Given that bisphosphonates act on enzymes called FPPS and GGPPS, which are upstream of Ras in the cell survival pathway, the researchers say that inhibiting these enzymes seems to be a more effective strategy for killing cancer cells.

The scientists used the bisphosphonate drug zoledronate in combination with hormone therapy in a recent clinical trial, and found it to significantly reduce the recurrence of breast cancer in pre-menopausal women with oestrogen-receptor-positive breast cancer.

Similar results were reported previously for hormone-refractory prostate cancer, they say.

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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're not going to go to breast, lung or other tissues," said lead researcher Eric Oldfield, a professor of Chemistry at the University of Illinois.

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"The new drugs are about 200 times more effective than the drugs used in recent clinical trials at killing tumour cells and in activating gamma delta T-cells to kill tumour cells. They also prevent tumour progression in mice much better than do existing bisphosphonate molecules," Oldfield said.

The study appears in the Journal of the American Chemical Society.

Source-ANI
SRM


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