TY  - JOUR
AU  - Müller, Michael
AU  - Rösch, Lisa
AU  - Najafi, Sara
AU  - Gatzweiler, Charlotte
AU  - Ridinger, Johannes
AU  - Gerloff, Xenia F
AU  - Jones, David T W
AU  - Baßler, Jochen
AU  - Kreth, Sina
AU  - Stainczyk, Sabine
AU  - Frese, Karen
AU  - Meder, Benjamin
AU  - Westermann, Frank
AU  - Milde, Till
AU  - Peterziel, Heike
AU  - Witt, Olaf
AU  - Oehme, Ina
TI  - Combining APR-246 and HDAC-Inhibitors: A Novel Targeted Treatment Option for Neuroblastoma.
JO  - Cancers
VL  - 13
IS  - 17
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2021-02020
SP  - 4476
PY  - 2021
N1  - #EA:B310#LA:B310#
AB  - 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
KW  - ROS (Other)
KW  - TP53 (Other)
KW  - histone deacetylases (Other)
KW  - pediatric tumors of the nervous system (Other)
KW  - precision medicine (Other)
KW  - response prediction biomarker (Other)
KW  - small molecule inhibitors (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34503286
DO  - DOI:10.3390/cancers13174476
UR  - https://inrepo02.dkfz.de/record/170569
ER  -