Niclosamide as a Promising Therapeutic Player in Human Cancer and Other Diseases

[Emily]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782559/
Wang Z, Ren J, Du J, Wang H, Liu J, Wang G. Niclosamide as a Promising Therapeutic Player in Human Cancer and Other Diseases. Int J Mol Sci. 2022 Dec 17;23(24):16116. doi: 10.3390/ijms232416116. PMID: 36555754; PMCID: PMC9782559.


Abstract

Niclosamide is an FDA-approved anthelmintic drug for the treatment of parasitic infections. However, over the past few years, increasing evidence has shown that niclosamide could treat diseases beyond parasitic diseases, which include metabolic diseases, immune system diseases, bacterial and viral infections, asthma, arterial constriction, myopia, and cancer. Therefore, we systematically reviewed the pharmacological activities and therapeutic prospects of niclosamide in human disease and cancer and summarized the related molecular mechanisms and signaling pathways, indicating that niclosamide is a promising therapeutic player in various human diseases, including cancer.

Keywords: niclosamide, FDA-approved drug, pharmacological activity, therapeutic prospect, cancer, disease

 

[Gert van der Hoek]

A Study of Niclosamide in Patients With Resectable Colon Cancer

ClinicalTrials.gov Identifier: NCT02687009

Recruitment Status : Terminated (low accrual) First Posted : February 22, 2016 Last Update Posted : February 19, 2020

 

[Emily]

https://www.nature.com/articles/s41598-021-85969-x
Parikh, M., Liu, C., Wu, CY. et al. Phase Ib trial of reformulated niclosamide with abiraterone/prednisone in men with castration-resistant prostate cancer. Sci Rep 11, 6377 (2021). https://doi.org/10.1038/s41598-021-85969-x


Abstract

Niclosamide has preclinical activity against a wide range of cancers. In prostate cancer, it inhibits androgen receptor variant 7 and synergizes with abiraterone. The approved niclosamide formulation has poor oral bioavailability. The primary objective of this phase Ib trial was to identify a maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of a novel reformulated orally-bioavailable niclosamide/PDMX1001 in combination with abiraterone and prednisone in men with castration-resistant prostate cancer (CRPC). Eligible patients had progressing CRPC, adequate end-organ function, and no prior treatment with abiraterone or ketoconazole. Patients were treated with escalating doses of niclosamide/PDMX1001 and standard doses of abiraterone and prednisone. Peak and trough niclosamide plasma levels were measured. Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and Prostate Cancer Working Group 2 criteria were used to evaluate toxicities and responses. Nine patients with metastatic CRPC were accrued, with no dose-limiting toxicities observed at all dose levels. The recommended Phase II dose of niclosamide/PDMX1001 was 1200 mg orally (PO) three times daily plus abiraterone 1000 mg PO once daily and prednisone 5 mg PO twice daily. Trough and peak niclosamide concentrations exceeded the therapeutic threshold of > 0.2 µM. The combination was well tolerated with most frequent adverse effects of diarrhea. Five out of eight evaluable patients achieved a PSA response; two achieved undetectable PSA and radiographic response. A novel niclosamide/PDMX1001 reformulation achieved targeted plasma levels when combined with abiraterone and prednisone, and was well tolerated. Further study of niclosamide/PDMX1001 with this combination is warranted.