# Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors

Source: https://onco.cc/key-papers/paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018/  
OnCo record `paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In mice, losing the KDM6A gene turned pancreatic tumours squamous and metastatic, especially in females, by switching on growth regulators including MYC, and a drug class that blocks BET proteins reversed the change.

## Summary

KDM6A, an X chromosome-encoded histone demethylase of the COMPASS-like complex, is frequently mutated across cancers. KDM6A loss induced squamous-like, metastatic pancreatic cancer selectively in females through deregulation of the COMPASS-like complex and aberrant activation of super-enhancers regulating delta-Np63, MYC and RUNX3. Tumours of this type in males had concomitant loss of UTY and KDM6A, pointing to demethylase-independent suppressor functions. KDM6A-deficient pancreatic cancer was selectively sensitive to BET inhibitors, which reversed squamous differentiation and restrained tumour growth in vivo.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Cancer Cell
- Year: 2018
- DOI: 10.1016/j.ccell.2018.02.003
- Authors: Andricovich J, Perkail S, Kai Y, et al.
- Findings: KDM6A loss drives squamous-like, metastatic tumours via super-enhancers at delta-Np63, MYC and RUNX3.; KDM6A-deficient tumours are selectively sensitive to BET inhibitors in vivo.
- What it means: It gives the 3 to 4% of KDM6A-mutant, squamous-programme tumours a mechanism and a candidate drug class.
- Caveats: Mouse and cell-line evidence only.; No clinical BET inhibitor trial in KDM6A-mutant pancreatic cancer has reported.

## Sources

- Andricovich et al., Cancer Cell 2018: KDM6A loss induces squamous-like pancreatic cancer: https://doi.org/10.1016/j.ccell.2018.02.003
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29533787/

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- targets: [KDM6A](https://onco.cc/targets/kdm6a/), [MYC](https://onco.cc/targets/myc-gene/)
- pathways: [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [MYC](https://onco.cc/pathways/myc/)
- journals: [Cancer Cell](https://onco.cc/journals/cancer-cell/)

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