Towards the first targeted therapy for triple-negative breast cancer: Repositioning of clofazimine
Towards the first targeted therapy for triple-negative breast cancer: Repositioning of clofazimine as a chemotherapy-compatible selective Wnt pathway inhibitor. https://www.ncbi.nlm.nih.gov/pubmed/30771433
"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."
From eurekalert: In addition, clofazimine is even more effective when administered in combination with doxorubicin, a conventional chemotherapeutic drug. Alexey Koval, a researcher at the CRTOH of the UNIGE at the Faculty of Biology and Medicine of the UNIL and co-first author of this study, analyses these results: "Clofazimine acts as an inhibitor of the Wnt signaling pathway: the sick cell can no longer divide, but does not die. Doxorubicin, on the other hand, kills cells that have stopped growing. A combination of great efficacy!" https://www.eurekalert.org/pub_releases/2019-03/udg-bct032819.php