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@ARTICLE{Farin:277774,
author = {H. Farin$^*$ and M. H. Mosa and B. Ndreshkjana and B. M.
Grebbin and B. Ritter and C. Menche and K. B. Kennel and P.
K. Ziegler and L. Szabo and J. Bollrath and D. Rieder and B.
E. Michels and A. Kress and M. Bozlar and T. Darvishi and S.
Stier and I.-M. Kur and K. Bankov and R. Kesselring$^*$ and
S. Fichtner-Feigl and B. Brune$^*$ and T. O. Goetze and
S.-E. Al-Batran and C. H. Brandts$^*$ and W. O. Bechstein
and P. J. Wild$^*$ and A. Weigert$^*$ and S. Muller and S.
Knapp$^*$ and Z. Trajanoski and F. R. Greten$^*$},
title = {{C}olorectal cancer organoid-stroma biobank allows
subtype-specific assessment of individualized therapy
responses.},
journal = {Cancer discovery},
volume = {13},
number = {10},
issn = {2159-8274},
address = {Philadelphia, Pa.},
reportid = {DKFZ-2023-01489},
pages = {2192-2211},
year = {2023},
note = {2023 Oct 5;13(10):2192-2211},
abstract = {In colorectal cancers (CRC) the tumor microenvironment
plays a key role for prognosis and therapy efficacy.
Patient-derived tumor organoids (PDTOs) show enormous
potential for preclinical testing, however, cultured tumor
cells lose important characteristics including the
'consensus molecular subtypes' (CMS). To better reflect the
cellular heterogeneity, we established the CRC
organoid-stroma biobank of matched PDTOs and
cancer-associated fibroblasts (CAFs) from 30 patients.
Context-specific phenotyping showed that xenotransplantation
or co-culture with CAFs improves the transcriptomic fidelity
and instructs subtype-specific stromal gene expression.
Furthermore, functional profiling in co-culture exposed
CMS4-specific therapeutic resistance to Gefitinib and SN-38
and prognostic expression signatures. Chemogenomic library
screening identified patient- and therapy-dependent
mechanisms of stromal resistance including MET as common
target. Our results demonstrate that CRC phenotypes are
encrypted in the cancer epithelium in a plastic fashion that
strongly depends on the context. Consequently, CAFs are
essential for faithful representation of molecular subtypes
and therapy responses ex vivo.},
cin = {FM01 / FR01},
ddc = {610},
cid = {I:(DE-He78)FM01-20160331 / I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37489084},
doi = {10.1158/2159-8290.CD-23-0050},
url = {https://inrepo02.dkfz.de/record/277774},
}