% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Breitkreutz:132788,
author = {I. Breitkreutz$^*$ and K. Podar$^*$ and V. Figueroa-Vazquez
and S. Wilhelm and P. J. Hayden and K. C. Anderson$^*$ and
M.-S. Raab$^*$},
title = {{T}he orally available multikinase inhibitor regorafenib
({BAY} 73-4506) in multiple myeloma.},
journal = {Annals of hematology},
volume = {97},
number = {5},
issn = {0939-5555},
address = {Berlin},
publisher = {Springer61936},
reportid = {DKFZ-2018-00432},
pages = {839-849},
year = {2018},
abstract = {A promising approach to the treatment of multiple myeloma
(MM) involves agents that target not only the myeloma cells
directly, but also the tumor microenvironment which promotes
tumor cell growth, angiogenesis, and MM bone disease. Here
we investigate the orally available multikinase inhibitor,
regorafenib (BAY 73-4506), for its therapeutic efficacy in
MM. Regorafenib is a potent inhibitor of angiogenic (VEGFR
1-3, PDGFR-b) as well as oncogenic (c-KIT, RET, FGFR, Raf)
kinases. We show that regorafenib induces apoptosis in all
MM cell lines at below clinically achievable concentrations.
Regorafenib overcomes the growth advantage conferred by a
stroma cell MM and an endothelial cell MM, co-culture
systems, and abrogates growth factor-stimulated MEK, ERK,
and AKT phosphorylation at nanomolar to micromolar
concentrations. Moreover, it inhibits endothelial cell
growth and tubule formation, abrogates both VEGF secretion
and VEGF-induced MM cell migration, inhibits
osteoclastogenesis, and shows synergistic cytotoxicity with
dexamethasone, the immunomodulatory drug pomalidomide, and
the p110δ inhibitor idelalisib. Most importantly,
regorafenib significantly delays tumor growth in a xenograft
mouse model of human MM. These results provide the rationale
for further clinical evaluation of regorafenib, alone and in
combination, in the treatment of MM.},
keywords = {Phenylurea Compounds (NLM Chemicals) / Protein Kinase
Inhibitors (NLM Chemicals) / Pyridines (NLM Chemicals) /
regorafenib (NLM Chemicals)},
cin = {G170},
ddc = {610},
cid = {I:(DE-He78)G170-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29359239},
doi = {10.1007/s00277-018-3237-5},
url = {https://inrepo02.dkfz.de/record/132788},
}