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A friend sends this article.
Scientists have found a way to trick cancer cells into committing suicide. The new synthetic compound, which removes a molecular safety catch that activates a natural executioner in the body's cells, could lead to better treatments of cancers including those affecting the lung, skin, breast, kidney and colon.The body has several defences against cells growing out of control and into tumours - one is to cause defective or dangerous cells to commit suicide. This natural process of cell death, called apoptosis, involves a protein called procaspase-3. When activated, procaspase-3 changes into an enzyme called caspase-3, which begins the cell death. In cancers, this mechanism is often faulty and cells can grow unchecked. Many types of cancer are resistant not only to the body's own signals for cell death but also to the chemotherapy drugs that try to mimic it.
But Paul Hergenrother, a chemist at the University of Illinois at Urbana-Champaign, has found a way around the natural biological process that kickstarts apoptosis - a synthetic molecule that directly activates procaspase-3. "This is the first in what could be a host of organic compounds with the ability to directly activate executioner enzymes."
His team screened more than 20,000 different compounds, looking for the one with the ability to turn procaspase-3 into caspase-3. The researchers called the successful molecule "procaspase activating compound number one" (PAC-1). The results are published today in Nature Chemical Biology.
The scientists found that PAC-1 killed many types of cancer cells, but how well it worked depended on the body's natural levels of procaspase-3. In lung cancer cells, for example, where levels of procaspase-3 were five times higher than normal, the new molecule worked well.
"It is now clear that many cancers have elevated concentrations of procaspase-3," wrote Prof Hergenrother in the Nature paper. "Others have heightened or reduced concentrations of procaspase-3 depending on the cancer subtype." He added that a systematic analysis of procaspase-3 concentrations in a variety of cancer types was needed to determine which cancers would be most amenable to treatment with a molecule such as PAC-1.
Testing cancers for procaspase-3 would lead to personalised treatments for cancer patients. "As such, the potential effectiveness of a compound such as PAC-1 could be assessed ... with a high degree of accuracy, and people with cancer could be pre-selected for treatment with a procaspase-3 activator based on the concentration of procaspase-3 in their tumour cells," said Prof Hergenrother. This personalised treatment is preferred to more general therapies because the amounts of drugs can be tailored to a person's condition, reducing the risk of side-effects often caused by chemotherapy.
Thanks, Tom. I think I'll look further into this.
Posted by The Vorlon at August 28, 2006 11:14 AM