Partitioning of cancer therapeutics in nuclear condensates
It is found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target, which suggests that selective partitioning and concentration of small molecules within condensate contributes to drug pharmacodynamics.
Abstract
<jats:title>Drug partitioning in nuclear condensates</jats:title> <jats:p> There is increasing interest in the function of phase-separated biomolecular condensates in cells because of their distinct properties and expanding roles in important biological processes. Klein <jats:italic>et al.</jats:italic> considered the fate of small-molecule therapeutics in the context of nuclear condensates (see the Perspective by Viny and Levine). They show that certain antineoplastic drugs have physicochemical properties that cause them to concentrate preferentially in condensates, both in vitro and in cancer cells. This property influences drug activity, and protein mutations that alter condensate formation can lead to drug resistance. Optimizing condensate partitioning may be valuable in developing improved therapeutics. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6497" page="1386" related-article-type="in-this-issue" vol="368" xlink:href="10.1126/science.aaz4427">1386</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6497" page="1314" related-article-type="in-this-issue" vol="368" xlink:href="10.1126/science.abc5318">1314</jats:related-article> </jats:p>