Niclosamide for Stage IV Cancer
Also known as: Niclocide
An FDA-approved anthelmintic that inhibits multiple oncogenic pathways simultaneously — Wnt, STAT3, NF-κB, and Notch.
Mechanism of Action
Niclosamide uncouples oxidative phosphorylation in mitochondria, inhibits Wnt/β-catenin transcriptional activity through degradation of β-catenin, blocks STAT3 phosphorylation (reducing survival signaling), and induces autophagy. Its multi-target profile makes it attractive for cancers with pathway redundancy where single-target inhibitors fail.
General mechanism: Anthelmintic. Uncouples oxidative phosphorylation. Wnt/β-catenin, STAT3, NF-κB, and Notch pathway inhibitor.
Current Evidence
Phase I/II trials for colorectal cancer and prostate cancer. Bioavailability is limited by poor oral absorption. Niclosamide ethanolamine formulations attempt to improve systemic exposure. Preclinical evidence is extensive across cancer types.
Clinical Status: Phase I/II trials for colorectal and prostate cancer. FDA-approved anthelmintic. Reformulation efforts ongoing.
Safety Profile
Well-established safety from decades of anthelmintic use. Poor oral bioavailability limits systemic exposure at current doses.
Key Research Questions
- Can reformulated niclosamide achieve therapeutic systemic concentrations?
- Which cancers with Wnt-pathway dependence are most vulnerable?
- Can niclosamide be combined with checkpoint inhibitors to overcome STAT3-mediated immune evasion?