TY  - INPR
A1  - Michaelis, Martin
A1  - Wass, Mark N.
A1  - Reddin, Ian
A1  - Voges, Yvonne
A1  - Rothweiler, Florian
A1  - Hehlgans, Stephanie
A1  - Cinatl, Jaroslav
A1  - Mernberger, Marco
A1  - Nist, Andrea
A1  - Stiewe, Thorsten
A1  - Rödel, Franz
A1  - Cinatl, Jindrich
T1  - Drug-adapted cancer cell lines reveal drug-induced heterogeneity and enable the identification of biomarker candidates for the acquired resistance setting
T2  - bioRxiv
N2  - Survivin is a drug target and the survivin suppressant YM155 a drug candidate for high-risk neuroblastoma. Findings from one YM155-adapted subline of the neuroblastoma cell line UKF-NB-3 had suggested that increased ABCB1 (mediates YM155 efflux) levels, decreased SLC35F2 (mediates YM155 uptake) levels, decreased survivin levels, and TP53 mutations indicate YM155 resistance. Here, the investigation of ten additional YM155-adapted UKF-NB-3 sublines only confirmed the roles of ABCB1 and SLC35F2. However, cellular ABCB1 and SLC35F2 levels did not indicate YM155 sensitivity in YM155-naïve cells, as indicated by drug response data derived from the Cancer Therapeutics Response Portal (CTRP) and the Genomics of Drug Sensitivity in Cancer (GDSC) databases. Moreover, the resistant sublines were characterised by a remarkable heterogeneity. Only seven sublines developed on-target resistance as indicated by resistance to RNAi-mediated survivin depletion. The sublines also varied in their response to other anti-cancer drugs. In conclusion, cancer cell populations of limited intrinsic heterogeneity can develop various resistance phenotypes in response to treatment. Therefore, individualised therapies will require monitoring of cancer cell evolution in response to treatment. Moreover, biomarkers can indicate resistance formation in the acquired resistance setting, even when they are not predictive in the intrinsic resistance setting.
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72691
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-726911
IS  - 2020.02.13.947374
ER  -