UNIGE document Scientific Article
previous document  unige:115677  next document
add to browser collection
Title

Towards the first targeted therapy for triple-negative breast cancer: Repositioning of clofazimine as a chemotherapy-compatible selective Wnt pathway inhibitor

Authors
Ahmed, Kamal
Published in Cancer Letters. 2019, vol. 449, p. 45-55
Abstract Wnt signaling is overactivated in triple-negative breast cancer (TNBC) and several other cancers, and its suppression emerges as an effective anticancer treatment. However, no drugs targeting the Wnt pathway exist on the market nor in advanced clinical trials. Here we provide a comprehensive body of preclinical evidence that an anti-leprotic drug clofazimine is effective against TNBC. Clofazimine specifically inhibits canonical Wnt signaling in a panel of TNBC cells in vitro. In several mouse xenograft models of TNBC, clofazimine efficiently suppresses tumor growth, correlating with in vivo inhibition of the Wnt pathway in the tumors. Clofazimine is well compatible with doxorubicin, exerting additive effects on tumor growth suppression, producing no adverse effects. Its excellent and well-characterized pharmacokinetics profile, lack of serious adverse effects at moderate (yet therapeutically effective) doses, its combinability with cytotoxic therapeutics, and the novel mechanistic mode of action make clofazimine a prime candidate for the repositioning clinical trials. Our work may bring forward the anti-Wnt targeted therapy, desperately needed for thousands of patients currently lacking targeted treatments.
Keywords Triple-negative breast cancerClofazimineWnt signalingTargeted therapyDrug combination
Identifiers
PMID: 30771433
Full text
Structures
Research group Voies de signalisation oncogéniques (998)
Projects Swiss cancer league KFS-2978-08-2012
Novartis MBR 17C153
Citation
(ISO format)
AHMED, Kamal et al. Towards the first targeted therapy for triple-negative breast cancer: Repositioning of clofazimine as a chemotherapy-compatible selective Wnt pathway inhibitor. In: Cancer Letters, 2019, vol. 449, p. 45-55. https://archive-ouverte.unige.ch/unige:115677

29 hits

23 downloads

Update

Deposited on : 2019-04-03

Export document
Format :
Citation style :