{"entity":{"id":"paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018","kind":"paper","name":"Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors","aka":[],"tldr":"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.","asOf":"2026-09-24","links":[{"label":"Andricovich et al., Cancer Cell 2018: KDM6A loss induces squamous-like pancreatic cancer","url":"https://doi.org/10.1016/j.ccell.2018.02.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29533787/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["kdm6a","myc-gene"],"drugs":[],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","myc"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2018,"doi":"10.1016/j.ccell.2018.02.003","pmid":"29533787","authors":"Andricovich J, Perkail S, Kai Y, et al.","paperType":"basic","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."],"whatItMeans":"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."],"changedPractice":false},"route":"/key-papers/paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"target":[{"id":"kdm6a","kind":"target","name":"KDM6A","route":"/targets/kdm6a/"},{"id":"myc-gene","kind":"target","name":"MYC","route":"/targets/myc-gene/"}],"pathway":[{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"}],"journal":[{"id":"cancer-cell","kind":"journal","name":"Cancer Cell","route":"/journals/cancer-cell/"}]}}