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New drug blocks bladder cancer gene

The bodily protein known as ‘Ral’ drives tumour growth and the spread of cancer from one part of the body to another. Unfortunately, currently there is no drug which can block its activity.

A study published in the medical journal ‘Nature’ has shown that scientists have found a novel way to approach and target the activation of these Ral proteins.

Dr Dan Theodorescu, the professor of Urology and Pharmacology at the University of Colorado Cancer Centre and the study’s senior researcher said, “When you want to keep an alligator from biting you, you can tie its mouth shut. We took another approach – we put a stick in its mouth to hold it open.”
By locating the inactive forms of the Ral protein, the research team have developed a way to bind the protein and keep the cavity in place and the protein itself inactive. The scientists used a handful of compound molecules to bind to the protein in order to reduce the Ral activation in lung cancer cells.The research team used advanced computer models and programmed to examine the structure of the Ral protein in its inactive form and compared it to its contrasting active form, looking for specific changes in its structure which could give them clues about what sort of elements and features helped encourage tumour growth and metastasis. The team found that the inactive form of the protein has a cavity which disappears when it becomes active – this was the ‘mouth of the alligator’ and now Dr Theodorescu and his colleagues needed to find the ‘stick’.

Further testing showed that the compounds’ restriction over the Ral protein meant that it slowed the cancer tumour cell growth – something which encourages the cancer to spread to other parts of the body. Even further testing showed that specific compound molecules managed to enter the tumour tissue and slow the growth of cancerous tumours within a matter of hours.

Scientists still need to refine the compounds that they have seen work against these types of cancers, as well as check for toxicity before determining the ideal way to transmit this treatment to the patient – orally or intravenously – before it becomes a mainstream and widely used treatment.

Theodorescu says, “We see this work as a valuable first step in the development of a novel class of therapeutic agents directed at Ral. [This research]…could in principle be used to discover drugs aimed at other proteins driving human disease as well.”

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