# SWI/SNF chromatin remodelling

Source: https://onco.cc/pathways/swi-snf-chromatin/  
OnCo record `swi-snf-chromatin` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A machine that opens and closes DNA so genes can be read. One in five cancers has a broken part (ARID1A, SMARCA4, PBRM1), and losing one part often creates a dependence on its twin, which is the basis for new synthetic-lethal drugs.

## Summary

SWI/SNF (BAF, PBAF, ncBAF) complexes remodel nucleosomes; subunits are mutated in ~20% of cancers: ARID1A (ovarian clear cell, endometrial, bladder), SMARCA4 (lung, SCCOHT), PBRM1 (clear-cell RCC), SMARCB1 (rhabdoid tumours, epithelioid sarcoma). Dependencies: SMARCA4-loss → SMARCA2 (degraders in trials), ARID1A-loss → EZH2/ATR/PARP, SMARCB1-loss → EZH2 (tazemetostat, withdrawn 2026 for safety). PBRM1 loss associates with IO response in RCC (debated). FHD-286 (BRM/BRG1 inhibitor) is in AML trials.

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- Analogy: A librarian who unlocks shelves on request. When one librarian is fired the other covers both shifts; fire the second and the library stops working. That second librarian is the drug target.
- Interventions: SMARCA2 degraders (PRT3789, PRT7732) in SMARCA4-mutant cancers (phase 1/2); EZH2 inhibition in SMARCB1-deficient tumours (tazemetostat withdrawn 2026); ATR/PARP inhibitors in ARID1A-mutant tumours (trials); FHD-286 in AML

## Notes

- Leading programmes: Kadoch (Dana-Farber/Broad) on SWI/SNF structure and Foghorn Therapeutics; Crabtree (Stanford); Roberts (St. Jude) on SMARCB1.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/SWI/SNF
- Centore, Sandoval, Soares, Kadoch & Chan, Mammalian SWI/SNF chromatin remodeling complexes (Trends in Genetics 2020): https://doi.org/10.1016/j.tig.2020.07.011

## Connected records

- cancers: [Atypical teratoid/rhabdoid tumour (ATRT)](https://onco.cc/cancers/atrt/), [Chordoma](https://onco.cc/cancers/chordoma/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Epithelioid sarcoma](https://onco.cc/cancers/epithelioid-sarcoma/), [Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma)](https://onco.cc/cancers/sinonasal/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/), [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/)
- targets: [ARID1A](https://onco.cc/targets/arid1a/), [ATR](https://onco.cc/targets/atr/), [EZH2](https://onco.cc/targets/ezh2/), [SMARCA2](https://onco.cc/targets/smarca2/), [SMARCA4](https://onco.cc/targets/smarca4/), [SMARCB1](https://onco.cc/targets/smarcb1/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/), [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/), [Stanford Health Care / Stanford Cancer Institute](https://onco.cc/institutions/stanford/)
- pathways: [Cancer stem cells & phenotypic plasticity](https://onco.cc/pathways/cancer-stem-cells-plasticity/), [DNA replication stress](https://onco.cc/pathways/replication-stress/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- key papers: [A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020/), [Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas](https://onco.cc/key-papers/paper-campbell-pan-lung-somatic-alterations-nat-genet-2016/), [Genomic analyses identify molecular subtypes of pancreatic cancer](https://onco.cc/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/), [Mammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies](https://onco.cc/key-papers/paper-centore-trends-genet/), [Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes](https://onco.cc/key-papers/paper-biankin-pancreatic-exomes-axon-guidance-nature-2012/), [The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer](https://onco.cc/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/)
- terms: [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/), [Hallmark (2022): non-mutational epigenetic reprogramming](https://onco.cc/terms/nonmutational-epigenetic-reprogramming/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)

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