TY  - JOUR
AU  - Beumers, Lukas
AU  - Vlachavas, Efstathios-Iason
AU  - Borgoni, Simone
AU  - Schwarzmüller, Luisa
AU  - Penso-Dolfin, Luca
AU  - Michels, Birgitta
AU  - Sofyali, Emre
AU  - Burmester, Sara
AU  - Heiss, Daniela
AU  - Wilhelm, Heike
AU  - Yarden, Yosef
AU  - Helm, Dominic
AU  - Will, Rainer
AU  - Goncalves, Angela
AU  - Wiemann, Stefan
TI  - Clonal heterogeneity in ER+ breast cancer reveals the proteasome and PKC as potential therapeutic targets.
JO  - npj Breast cancer
VL  - 9
IS  - 1
SN  - 2374-4677
CY  - London
PB  - Nature Publ. Group
M1  - DKFZ-2023-02535
SP  - 97
PY  - 2023
N1  - #EA:B050#LA:B050#
AB  - Intratumoral heterogeneity impacts the success or failure of anti-cancer therapies. Here, we investigated the evolution and mechanistic heterogeneity in clonal populations of cell models for estrogen receptor positive breast cancer. To this end, we established barcoded models of luminal breast cancer and rendered them resistant to commonly applied first line endocrine therapies. By isolating single clones from the resistant cell pools and characterizing replicates of individual clones we observed inter- (between cell lines) and intra-tumor (between different clones from the same cell line) heterogeneity. Molecular characterization at RNA and phospho-proteomic levels revealed private clonal activation of the unfolded protein response and respective sensitivity to inhibition of the proteasome, and potentially shared sensitivities for repression of protein kinase C. Our in vitro findings are consistent with tumor-heterogeneity that is observed in breast cancer patients thus highlighting the need to uncover heterogeneity at an individual patient level and to adjust therapies accordingly.
LB  - PUB:(DE-HGF)16
C6  - pmid:38042915
C2  - pmc:PMC10693625
DO  - DOI:10.1038/s41523-023-00604-4
UR  - https://inrepo02.dkfz.de/record/285945
ER  -