{"entity":{"id":"idea-bio1-condensate-disruptors","kind":"idea","name":"Break up the liquid droplets where oncogenic transcription happens","aka":[],"tldr":"Some cancer-driving proteins gather into droplet-like blobs inside the nucleus to switch genes on. Drugs that dissolve those blobs might switch the cancer programme off.","summary":"Transcriptional condensates concentrate MYC, fusion oncoproteins, mediator complex and RNA polymerase at super-enhancers. Certain drugs, including some antineoplastics, concentrate selectively in condensates, and condensate-modulating chemotypes have been reported. A dedicated screen using condensate-specific reporters (optoDroplet or in vitro reconstitution with labelled scaffolds) could identify compounds that selectively dissolve oncogenic condensates while sparing normal ones.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["epigenetic-drugs"],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber","broad-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Compounds that dissolve oncoprotein condensates suppress super-enhancer-driven transcription and kill condensate-dependent tumour cells at concentrations that do not affect housekeeping transcription.","rationale":"Condensate biology is a general mechanism for transcription factors that lack pockets, and drug partitioning into condensates has been shown to affect potency, so the physics is at least addressable.","test":"Reconstituted condensate screens with orthogonal cellular validation in an EWS-FLI1 and a MYC-amplified model, with transcriptomic evidence of selective super-enhancer target loss.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":9},"route":"/ideas/idea-bio1-condensate-disruptors/","neighbours":{"technology":[{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"}],"institution":[{"id":"broad-institute","kind":"institution","name":"Broad Institute of MIT and Harvard","route":"/institutions/broad-institute/"},{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","route":"/key-papers/paper-dang-nat-rev-cancer/"}]}}