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Examples
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Because hemiasterlin compounds are being tested as a way to fight multi-drug resistance, this newly discovered resistance effect is problematic, the researchers said.
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The UT Southwestern researchers sought to pin down the action of hemiasterlin, so they worked with the tiny research worm C. elegans, which is often used for genetic studies but not often used to test drugs.
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The researchers created a large population of mutant worms and isolated eight that were resistant to derivatives of hemiasterlin.
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"One of the properties of hemiasterlin that makes it attractive as a potential therapeutic is that it remains very toxic for cancer cells that express the multi-drug resistance protein, which is a major mechanism of drug resistance in cancer," said Dr. Roth.
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The drug is a derivative of a compound called hemiasterlin.
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The mutation also made these worms resistant not only to hemiasterlin but also to several other anti-cancer drugs that interfere with tubulin.
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Derivatives of hemiasterlin are being tested as anti-cancer therapies, with one already in clinical study.
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However, hemiasterlin bypasses this pump altogether and kills cancer cells by preventing them from dividing.
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Further studies will focus on the other strains of mutant worms to determine whether the anti-cancer drugs that attack tubulin use mechanisms similar to hemiasterlin.
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