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

Published inCancer Letters, vol. 449, p. 45-55
Publication date2019
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 cancer
  • Clofazimine
  • Wnt signaling
  • Targeted therapy
  • Drug combination
Funding
  • Autre - Swiss cancer league KFS-2978-08-2012
  • Autre - 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. doi: 10.1016/j.canlet.2019.02.018
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Article (Accepted version)
Identifiers
ISSN of the journal0304-3835
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