%0 Journal Article
%A Müller, Michael
%A Rösch, Lisa
%A Najafi, Sara
%A Gatzweiler, Charlotte
%A Ridinger, Johannes
%A Gerloff, Xenia F
%A Jones, David T W
%A Baßler, Jochen
%A Kreth, Sina
%A Stainczyk, Sabine
%A Frese, Karen
%A Meder, Benjamin
%A Westermann, Frank
%A Milde, Till
%A Peterziel, Heike
%A Witt, Olaf
%A Oehme, Ina
%T Combining APR-246 and HDAC-Inhibitors: A Novel Targeted Treatment Option for Neuroblastoma.
%J Cancers
%V 13
%N 17
%@ 2072-6694
%C Basel
%I MDPI
%M DKFZ-2021-02020
%P 4476
%D 2021
%Z #EA:B310#LA:B310#
%X APR-246 (Eprenetapopt/PRIMA-1Met) is a very potent anti-cancer drug in clinical trials and was initially developed as a p53 refolding agent. As an alternative mode of action, the elevation of reactive oxygen species (ROS) has been proposed. Through an in silico analysis, we investigated the responses of approximately 800 cancer cell lines (50 entities; Cancer Therapeutics Response Portal, CTRP) to APR-246 treatment. In particular, neuroblastoma, lymphoma and acute lymphocytic leukemia cells were highly responsive. With gene expression data from the Cancer Cell Line Encyclopedia (CCLE; n = 883) and patient samples (n = 1643) from the INFORM registry study, we confirmed that these entities express low levels of SLC7A11, a previously described predictive biomarker for APR-246 responsiveness. Combining the CTRP drug response data with the respective CCLE gene expression profiles, we defined a novel gene signature, predicting the effectiveness of APR-246 treatment with a sensitivity of 90
%K ROS (Other)
%K TP53 (Other)
%K histone deacetylases (Other)
%K pediatric tumors of the nervous system (Other)
%K precision medicine (Other)
%K response prediction biomarker (Other)
%K small molecule inhibitors (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34503286
%R 10.3390/cancers13174476
%U https://inrepo02.dkfz.de/record/170569