BioWorld International Correspondent

LONDON - A new compound that could effectively treat those types of prostate and breast cancer that do not depend on hormones for their growth may be available within a decade.

Researchers have used the compound, known as STX140, to treat tumors in an animal model of hormone-independent prostate cancer. STX140 completely inhibited tumor growth, without causing any weight loss in the animals.

The same study showed that it was possible to give STX140 orally on a daily basis without adverse side effects.

Simon Newman, research associate at Imperial College London, told BioWorld International: "Most drugs of this class are so toxic that they cannot be given regularly, but STX140 is one of the few examples of a drug of this type that can be given on a regular basis, therefore maintaining exposure of the tumor to the drug."

By contrast, he added, related drugs such as taxanes have to be given at three-weekly intervals for the treatment of human cancers, which gives the tumor time to recover and become resistant before the next dose.

Newman and his colleagues have published their findings on STX140 in a paper in the Nov. 20, 2007, online publication The British Journal of Cancer, titled: "The therapeutic potential of a series of orally bioavailable anti-angiogenic microtubule disruptors as therapy for hormone-independent prostate and breast cancers."

Concluding the paper, Newman and his colleagues wrote: "STX140 is envisaged to enter the clinic in 2008."

The paper described the evaluation of a series of compounds being developed by Sterix Ltd, originally a spinout company from Imperial College London and Bath University, and now part of the IPSEN group.

Newman and colleagues, collaborating with chemists at the University of Bath, UK, had identified compounds that killed cancer cells by disrupting their microtubules - filamentous structures within the cell that help to build the mitotic spindle.

Unlike taxanes, which bind to microtubules and stabilize them, causing the cell to become "stuck" at a point in the cell division cycle, the compounds being investigated by Newman's group have the effect of destabilizing the microtubules. The end result is very similar. Cell division cannot continue, and the cell undergoes apoptosis.

"There are many treatments for early stage hormone-dependent prostate cancer," Newman said, "but very few efficacious treatments for hormone-independent prostate cancer, and the same is true for hormone-independent breast cancer. We set out to test our drugs using a preclinical mouse model of prostate cancer, and found that we got excellent efficacy with STX140."

The researchers gave STX140 to the mice orally every day for 60 days. Five out of eight tumors shrank in size, with two disappearing completely after 88 days. The three tumors that did not get smaller responded to the drug by staying the same size.

Experiments showed that STX140 was more effective than taxanes tested on the same type of tumor model.

"This paper answers three important questions," Newman said. "It shows that the compound can be given orally, and that it can be given on a regular basis. It is also highly efficacious in both the hormone-independent breast cancer model and the hormone-independent prostate cancer model.

"We hope that STX140 will enter clinical trials so that we can test whether this treatment will be effective in humans. If the trial results reflect what our lab tests show, we could produce a treatment for cancer patients resistant to hormone therapy, hopefully with fewer side effects than conventional drugs," he added.

Lesley Walker, director of cancer information at Cancer Research UK, which owns the British Journal of Cancer, said: "Research into how to overcome resistance to cancer drugs is vitally important, as this is a common problem that affects the treatment of many people with cancer. Building on existing drugs to create smarter targeted therapies is an exciting field of cancer research. Further tests are needed before we can tell if this drug can be used in people, but many thousands of patients stand to benefit from treatments that beat the mechanisms involved in resistance to cancer drugs."

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