Partitioning of cancer therapeutics in nuclear condensates

TLDR

Phase‑separated nuclear condensates are increasingly studied for their distinct properties and roles in biology, and the fate of small‑molecule therapeutics within these condensates has become a key research focus. The study aims to optimize drug partitioning into nuclear condensates to enhance therapeutic development. The authors found that some antineoplastic drugs preferentially concentrate in nuclear condensates, affecting drug activity and that mutations altering condensate formation can confer drug resistance. Klein et al., Science, this issue p.

Abstract

Drug partitioning in nuclear condensates 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 et al. 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. Science , this issue p. 1386 ; see also p. 1314