# Break up the liquid droplets where oncogenic transcription happens

Source: https://onco.cc/ideas/idea-bio1-condensate-disruptors/  
OnCo record `idea-bio1-condensate-disruptors` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017): https://doi.org/10.1038/nrc.2017.36

## Connected records

- technologies: [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/), [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- key papers: [Drugging the 'undruggable' cancer targets](https://onco.cc/key-papers/paper-dang-nat-rev-cancer/)

---
JSON: https://onco.cc/api/v1/entities/idea-bio1-condensate-disruptors.json