P2/3, N=210, Recruiting, Hyundai Bioscience Co., Ltd.

Pharmacologic targeting of NDUFS4 using the niclosamide analog ARVib-7 phenocopied genetic depletion, suppressing mitochondrial respiration and enhancing olaparib efficacy to inhibit the growth of resistant spheroids. These findings identify NDUFS4 as a key mediator of PARPi resistance and a therapeutic vulnerability in advanced prostate cancer. Targeting NDUFS4 disrupts OxPhos and induces ferroptosis, providing a strong rationale for combination strategies with PARPis to overcome drug resistance.

It also induced significantly greater cytotoxicity than sorafenib ( p<0.05 ) in the PDO. Mechanistically, SSL-0024 suppressed major oncogenic pathways including AKT-mTOR-STAT3, RAF, and Wnt/β-catenin. SSL-0024 overcomes key pharmacokinetic limitations of niclosamide while maintaining potent anti-tumor activity, supporting its further development as an orally bioavailable therapeutic candidate for HCC.

P1, N=14, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2028

Pharmacologic targeting of NDUFS4 using the niclosamide analog ARVib-7 phenocopied genetic depletion, suppressing mitochondrial respiration and enhancing olaparib efficacy to inhibit the growth of resistant spheroids. These findings identify NDUFS4 as a key mediator of PARPi resistance and a therapeutic vulnerability in advanced prostate cancer. Targeting NDUFS4 disrupts oxidative phosphorylation and induces ferroptosis, providing a strong rationale for combination strategies with PARP inhibitors to overcome drug resistance.

These findings identify Niclosamide as a potent dual STAT1/STAT3 inhibitor capable of reversing IFN-γ- and hypoxia-driven immune evasion. Repurposing Niclosamide may represent a promising strategy to enhance the efficacy of immune checkpoint blockade in solid tumors.

The findings herein demonstrated that mitochondrial uncouplers inhibit MSCP through FTO-dependent m6A demethylation. This work identified mitochondrial uncoupling as a novel and promising therapeutic approach for promoting m6A demethylation and targeting MSCP in metastatic breast cancer.

P1, N=35, Completed, Immunome, Inc. | Active, not recruiting --> Completed

Canonical NF-κB signaling is mechanistically related to UM cell survival, proliferation, and migration, as shown by pharmacologic inhibition like BAY11-7082, and niclosamide and genetic modulation like microRNA-9. NF-κB signaling, particularly the canonical branch, is required for UM malignancy, while noncanonical signaling is linked with high-risk features. Branch-specific genetic manipulations and clinically relevant models should be employed in future research to maximize therapeutic strategies.

Concurrently, VEGF downregulation and p53 upregulation reflected additional anti-angiogenic and pro-apoptotic effects. Collectively, the lactoferrin-functionalized Nic-NLC produced the most robust antitumor response, with superior ferroptosis induction, redox modulation, and anti-angiogenic activity.

Notably, the predicted metformin plasma Cmax remained within a safe therapeutic window at the 100 mg/kg combination dose but exceeded a safety threshold at 200 mg/kg. By integrating in vivo efficacy testing with quantitative modeling, our study identified the 100 mg/kg combination of niclosamide and metformin as the optimal dose for chemoprevention in a murine FAP model, providing a strong rationale for future clinical translation in FAP management.

Our research revealed comprehensive metabolic alterations in gastric cancer, including upregulated lactate metabolism that promotes tumorigenesis via the lactate shuttle. Niclosamide targets the m6A methylation regulatory protein YTHDF2, which influences genes related to metabolism, indicating its potential as a prospective treatment for GC.