Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Wnt signaling is crucial in various cancers, including breast, colon, ovarian, and liver cancers.
• Targeted therapies for the Wnt pathway are currently unavailable.
• Clofazimine, an anti-mycobacterium drug, was previously identified as a Wnt signaling inhibitor in triple-negative breast cancer (TNBC).

Purpose of the Study:

• To investigate the efficacy of clofazimine in a broader range of Wnt-dependent cancers.
• To establish the correlation between clofazimine's effectiveness and Wnt pathway activation levels.
• To explore the influence of cancer mutational spectrum on drug response.

Main Methods:

• Utilized a panel of cell lines from hepatocellular carcinoma, glioblastoma, colorectal, and ovarian cancers.
• Assessed clofazimine's ability to inhibit Wnt signaling and cell proliferation in these diverse cancer types.
• Correlated drug efficacy with basal Wnt pathway activation and cancer-specific mutations.

Main Results:

• Clofazimine demonstrated efficacy across multiple Wnt-dependent cancer types.
• Drug effectiveness correlated positively with basal Wnt pathway activation levels.
• The cancer mutational spectrum influenced clofazimine's inhibitory activity.

Conclusions:

• Clofazimine shows potential as a Wnt pathway-targeted therapy for various cancers.
• The study provides a basis for patient stratification in future clofazimine clinical trials.
• This research may lead to novel Wnt-targeted treatments for diverse malignancies.