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@ARTICLE{Zhou:282686,
author = {X. Zhou and J. An and R. Kurilov$^*$ and B. Brors$^*$ and
K. Hu and T. Peccerella and S. Roessler and K. Pfütze$^*$
and A. Schulz$^*$ and S. Wolf$^*$ and N. Hohmann and D.
Theile and M. Sauter and J. Burhenne and S. Ei and U. Heger
and O. Strobel and S. T. Barry and C. Springfeld and C.
Tjaden and F. Bergmann and M. Büchler and T. Hackert and F.
Fortunato and J. P. Neoptolemos and P. Bailey},
title = {{P}ersister cell phenotypes contribute to poor patient
outcomes after neoadjuvant chemotherapy in {PDAC}.},
journal = {Nature cancer},
volume = {4},
number = {9},
issn = {2662-1347},
address = {London},
publisher = {Nature Research},
reportid = {DKFZ-2023-01832},
pages = {1362-1381},
year = {2023},
note = {#EA:B330# / 2023 Sep;4(9):1362-1381},
abstract = {Neoadjuvant chemotherapy can improve the survival of
individuals with borderline and unresectable pancreatic
ductal adenocarcinoma; however, heterogeneous responses to
chemotherapy remain a significant clinical challenge. Here,
we performed RNA sequencing (n = 97) and multiplexed
immunofluorescence (n = 122) on chemo-naive and
postchemotherapy (post-CTX) resected patient samples
(chemoradiotherapy excluded) to define the impact of
neoadjuvant chemotherapy. Transcriptome analysis combined
with high-resolution mapping of whole-tissue sections
identified GATA6 (classical), KRT17 (basal-like) and
cytochrome P450 3A (CYP3A) coexpressing cells that were
preferentially enriched in post-CTX resected samples. The
persistence of GATA6hi and KRT17hi cells post-CTX was
significantly associated with poor survival after
mFOLFIRINOX (mFFX), but not gemcitabine (GEM), treatment.
Analysis of organoid models derived from chemo-naive and
post-CTX samples demonstrated that CYP3A expression is a
predictor of chemotherapy response and that CYP3A-expressing
drug detoxification pathways can metabolize the prodrug
irinotecan, a constituent of mFFX. These findings identify
CYP3A-expressing drug-tolerant cell phenotypes in residual
disease that may ultimately inform adjuvant treatment
selection.},
cin = {B330 / HD01 / B340 / W190},
ddc = {610},
cid = {I:(DE-He78)B330-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B340-20160331 / I:(DE-He78)W190-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37679568},
doi = {10.1038/s43018-023-00628-6},
url = {https://inrepo02.dkfz.de/record/282686},
}