A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer

• Published in: PloS one Vol. 13; no. 6; p. e0198389
• Main Authors: Schweizer, Michael T., Haugk, Kathleen, McKiernan, Jožefa S., Gulati, Roman, Cheng, Heather H., Maes, Jessica L., Dumpit, Ruth F., Nelson, Peter S., Montgomery, Bruce, McCune, Jeannine S., Plymate, Stephen R., Yu, Evan Y.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2018; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Alternative splicing; Androgen receptors; Androgens; Anthelmintics; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Augmented reality; Benzamides; Bioavailability; Biology; Biology and Life Sciences; Cancer; Castration; Cell Proliferation - drug effects; Colitis; Combination drug therapy; Constraining; Diarrhea; Dosage and administration; Dose-Response Relationship, Drug; Drug dosages; Drug resistance; Drug Resistance, Neoplasm - drug effects; Drug therapy; Enzalutamide; Humans; Ligands; Male; Maximum Tolerated Dose; Medical research; Medicine; Medicine and Health Sciences; Metastases; Metastasis; Methods; Middle Aged; Mutation; Nausea; Neoplasm Metastasis; Niclosamide; Niclosamide - administration & dosage; Niclosamide - adverse effects; Niclosamide - pharmacokinetics; Nitriles; Oncology; Patients; Pharmacokinetics; Pharmacology; Phenylthiohydantoin - administration & dosage; Phenylthiohydantoin - adverse effects; Phenylthiohydantoin - analogs & derivatives; Phenylthiohydantoin - pharmacokinetics; Prostate; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - metabolism; Prostatic Neoplasms, Castration-Resistant - pathology; Research and Analysis Methods; Safety; Testing; Toxicity; Tumor cells; Vomiting; Wnt protein; United States; United States > US; California; Puget Sound

Niclosamide, an FDA-approved anti-helminthic drug, has activity in preclinical models of castration-resistant prostate cancer (CRPC). Potential mechanisms of action include degrading constitutively active androgen receptor splice variants (AR-Vs) or inhibiting other drug-resistance pathways (e.g., W...