@misc{10481/70309,
year = {2021},
month = {7},
url = {http://hdl.handle.net/10481/70309},
abstract = {Despite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex
commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient
tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with
SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to
the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired
transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX
and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its
inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice
orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell
carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In
this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be
exploited for treating SMARCA4-mutant cancer patients.},
organization = {Spanish Ministry of Economy and Competitivity-MINECO	SAF-2017-82186R	
PI19/01320},
organization = {Fundacion Cientifica of the Asociacion Espanola Contra el Cancer (AECC)	GCB14142170MONT},
organization = {Department of Health of the Generalitat de Catalunya	2014SGR364},
organization = {Juan de la Cierva postdoctoral contract	IJCI-2016-28201},
organization = {AECC research contract	INVES19045ROME},
organization = {Spanish MINECO	PRE2018-084624	
BES-2015-072204	
FPU17/00067},
organization = {Instituto de Salud Carlos III
European Commission	CM17/00180},
organization = {European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Actions grant agreement	799850},
publisher = {Nature},
title = {SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade},
doi = {10.1038/s41467-021-24618-3},
author = {Romero, Octavio A. and Andrades Delgado, Álvaro and Medina Vico, Pedro Pablo},
}