Leveraging disulfiram to treat cancer: Mechanisms of action, delivery strategies, and treatment regimens

Yao Lu; Qingqing Pan; Wenxia Gao; Yuji Pu; Kui Luo; Bin He; Zhongwei Gu

doi:10.1016/j.biomaterials.2021.121335

Leveraging disulfiram to treat cancer: Mechanisms of action, delivery strategies, and treatment regimens

Biomaterials. 2022 Feb:281:121335. doi: 10.1016/j.biomaterials.2021.121335. Epub 2021 Dec 28.

Authors

Yao Lu¹, Qingqing Pan², Wenxia Gao³, Yuji Pu⁴, Kui Luo⁵, Bin He¹, Zhongwei Gu⁵

Affiliations

¹ National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China.
² School of Preclinical Medicine, Chengdu University, Chengdu, China.
³ College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou, 325027, China.
⁴ National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China. Electronic address: yjpu@scu.edu.cn.
⁵ Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Functional and Molecular Imaging Key Laboratory of Sichuan Province, Sichuan University, Chengdu, 610041, China.

PMID: 34979419
DOI: 10.1016/j.biomaterials.2021.121335

Abstract

Disulfiram (DSF) has been used as an alcoholism drug for 70 years. Recently, it has attracted increasing attention owing to the distinguished anticancer activity, which can be further potentiated by the supplementation of Cu²⁺. Although encouraging anticancer results are obtained in lab, the clinical outcomes of oral DSF are not satisfactory, which urges an in-depth understanding of the underlying mechanisms, bottlenecks, and proposal of potential methods to address the dilemma. In this review, a critical summarization of various molecular biological anticancer mechanisms of DSF/Cu²⁺ is provided and the predicament of orally delivering DSF in clinical oncotherapy is explained by the metabolic barriers. We highlight the recent advances in the DSF/Cu²⁺ delivery strategies and the emerging treatment regimens for cancer treatment. Last but not the least, we summarize the clinical trials regarding DSF and make a prospect of DSF/Cu-based cancer therapy.

Keywords: Anticancer mechanism; Anticancer therapy; Copper; Disulfiram; Drug delivery.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cell Line, Tumor
Copper / pharmacology
Disulfiram* / pharmacology
Disulfiram* / therapeutic use
Humans
Neoplasms* / drug therapy

Substances

Copper
Disulfiram