New drug delivery route to tumours

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  • Published: Aug 17, 2014
  • Author: Steve Down
  • Channels: Proteomics
thumbnail image: New drug delivery route to tumours

Scientists in the US have unearthed a novel route for delivering anti-tumour drugs directly to their targets. It takes advantage of the fact that one particular protein, annexin A1, is concentrated in the caveolae of tumour cells, but not healthy cells, so acting as a target for a specific antibody.

In recent years, there have been many reports of so-called smart anticancer drugs designed to attack a specific target within the body. However, in practice, they don’t live up to their reputation with large, often near toxic doses required to be effective. Now, Jan Schnitzer and colleagues from the Proteogenomics Research Institute for Systems Medicine and the Sidney Kimmel Cancer Center, both in San Diego, have found an alternative route which promises to be more successful.

Writing in Nature Medicine, they described how they used a proteomics approach to reveal that a modified form of annexin A1 which is cleaved at Lys-26, was concentrated in the small microdomains of cells called calveolae at the blood-tumour interface. A second protein, caveolin 1, was also more abundant in the caveolae near tumours.

The team generated fluorescently-labelled antibodies for this form of annexin A1, which they called tannexin, which showed that the protein crossed rapidly into the tumour and spread through it. This effect was observed in both humans and mice for breast, prostate and lung tumours. The effect was specific to tannexin because the uptake of other antibodies in the tumours was at least 100-fold less.

So, this discovery opens up a new route to take drugs right into tumours to target them, using modified antibodies. "Much work still needs to be done to both map expression and function at key rodent and human interfaces in vivo and establish to what degree the caveolae pumping system is useful in studying and treating tumours," said the researchers. "A much-needed and long-awaited portal or door has been identified to exist. This door may create new hope that the theoretical impact of targeted molecular medicine envisioned decades ago may someday be realized."

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