Genomics

Dataset Information

156

DNA Seq data: biopy samples from patients pre- and post- treated with Vorinostat


ABSTRACT: BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance, which is frequently caused by reactivation of the Mitogen Activated Protein Kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor (HDACi) vorinostat represses SLC7A11 that leads to a lethal increase in the already elevated levels of ROS in drug-resistant cells, thereby causing selective apoptotic death of only the drug resistant tumor cells. Consistently, treatment of BRAF inhibitor-resistant melanoma with HDACi in mice results in a dramatic tumor regression. In a study in patients with advanced BRAF+MEK inhibitor resistant melanoma, we find that HDACi can selectively ablate drug-resistant tumor cells, providing clinical proof of concept for the novel therapy identified here. DNA Seq data: biopy samples from patients pre- and post- treated with Vorinostat; check mutations related to MAPKi-resistance Overall design: one replicate of DNA _178 gene panel , paired end, patient samples pre-post vorinostat treated

INSTRUMENT(S): Illumina HiSeq 2500 (Homo sapiens)

SUBMITTER: Liqin Wang  

PROVIDER: GSE111140 | GEO | 2018-04-18

REPOSITORIES: GEO

altmetric image

Publications


BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance that is frequently caused by reactivation of the mitogen activated protein kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the hi  ...[more]

Similar Datasets

| GSE110948 | GEO
2015-08-26 | E-GEOD-45558 | ArrayExpress
2016-06-01 | E-GEOD-58421 | ArrayExpress
2014-04-21 | E-GEOD-49430 | ArrayExpress
| GSE99867 | GEO
2014-09-19 | E-GEOD-61544 | ArrayExpress
| GSE64550 | GEO
| GSE73737 | GEO
2015-09-16 | E-GEOD-68453 | ArrayExpress
2014-12-03 | E-GEOD-61992 | ArrayExpress