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@ARTICLE{Kbler:304084,
author = {K. Kübler$^*$ and A. Nardone and S. Anand and D. Gurevich
and J. Gao and M. Droog and F. Hermida-Prado and T. Akhshi
and A. Feiglin and A. S. Feit and G. Cohen Feit and G.
Dackus and M. Pun and Y. Kuang and J. Cha and M. Miller and
S. Gregoricchio and M. Lanfermeijer and S. Cornelissen and
W. J. Gibson and C. P. Paweletz and E. M. Van Allen and F.
E. van Leeuwen and P. M. Nederlof and Q.-D. Nguyen and M. J.
E. Mourits and M. Radovich and I. Leshchiner and C. Stewart
and U. A. Matulonis and W. Zwart and Y. E. Maruvka and G.
Getz and R. Jeselsohn},
title = {{T}amoxifen induces {PI}3{K} activation in uterine cancer.},
journal = {Nature genetics},
volume = {57},
number = {9},
issn = {1061-4036},
address = {London},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {DKFZ-2025-01752},
pages = {2192-2202},
year = {2025},
note = {2025 Sep;57(9):2192-2202},
abstract = {Mutagenic processes and clonal selection contribute to the
development of therapy-associated secondary neoplasms, a
known complication of cancer treatment. The association
between tamoxifen therapy and secondary uterine cancers is
uncommon but well established; however, the genetic
mechanisms underlying tamoxifen-driven tumorigenesis remain
unclear. We find that oncogenic PIK3CA mutations, common in
spontaneously arising estrogen-associated de novo uterine
cancer, are significantly less frequent in
tamoxifen-associated tumors. In vivo, tamoxifen-induced
estrogen receptor stimulation activates phosphoinositide
3-kinase (PI3K) signaling in normal mouse uterine tissue,
potentially eliminating the selective benefit of
PI3K-activating mutations in tamoxifen-associated uterine
cancer. Together, we present a unique pathway of
therapy-associated carcinogenesis in which tamoxifen-induced
activation of the PI3K pathway acts as a non-genetic driver
event, contributing to the multistep model of uterine
carcinogenesis. While this PI3K mechanism is specific to
tamoxifen-associated uterine cancer, the concept of
treatment-induced signaling events may have broader
applicability to other routes of tumorigenesis.},
cin = {BE01},
ddc = {570},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40846762},
doi = {10.1038/s41588-025-02308-w},
url = {https://inrepo02.dkfz.de/record/304084},
}