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The Evolving Role of Disulfiram in Radiobiology and the Treatment of Breast Cancer.

ABSTRACT: Disulfiram (DSF), also known as "Antabuse", has been widely used in clinical practice to treat alcoholism. In the past decades, both in vivo and in vitro experiments showed that DSF has strong anti-cancer activity, there were some clinical studies indicated the administration of this drug was associated with favorable survival in breast cancer. It is also evident that DSF has a radioprotective effect on normal cells and could be utilized during the course of radiation therapy. Moreover, increasing evidences demonstrated the role of DSF in enhancing the radiosensitivity of tumor cells in number of alternative mechanisms. Recent studies have also elaborated the anticancer mechanism of DSF in tumor cells. This review summarizes the anticancer activity of DSF both in preclinical studies and clinical trials, focuses on the advances of this drug in radiobiology and the treatment of breast cancer, and reveals the promising of repurposing DSF as a novel radiosensitizer and radioprotector in further clinical trials.

SUBMITTER: Wang R

PROVIDER: S-EPMC7569069 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Evolving Role of Disulfiram in Radiobiology and the Treatment of Breast Cancer.

Wang Rui R Shen Jun J Yan Huanhuan H Gao Xitao X Dong Tianfu T Wang Peishun P Zhou Jun J

OncoTargets and therapy 20201014

Disulfiram (DSF), also known as "Antabuse", has been widely used in clinical practice to treat alcoholism. In the past decades, both in vivo and in vitro experiments showed that DSF has strong anti-cancer activity, there were some clinical studies indicated the administration of this drug was associated with favorable survival in breast cancer. It is also evident that DSF has a radioprotective effect on normal cells and could be utilized during the course of radiation therapy. Moreover, increasi ...[more]

PMID: 33116623

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Project description:Antibody-drug conjugates (ADCs) are a class of antineoplastic agents whose structure is composed of three main components: a monoclonal antibody (mAB) targeting a specific target antigen, a cytotoxic payload, and a linker binding the antibody to the payload. By combining the specificity of mABs with the high potency of the payloads, ADCs constitute a smart drug delivery system with improved therapeutic index. After recognition and binding of the mAB to its target surface antigen, ADCs are internalized by endocytosis by the tumor cell, releasing the payloads into the cytoplasm, where they exert their cytotoxic activity, eventually leading to cell death. The composition of some of the new ADCs confers additional functional properties that allow expanding their activity to neighboring cells not expressing the target antigen, constituting a valuable strategy to overcome tumor heterogeneity. Some of these 'off-target effects', such as the bystander effect, are possibly the mechanism underlying the antitumor activity demonstrated in patients with low expression of the target antigens, which represents an important paradigm shift in anticancer targeted therapy. Three ADCs are currently approved for the treatment of breast cancer (BC); two anti-HER2 (human epidermal growth factor receptor 2) ADCs (trastuzumab emtansine and trastuzumab deruxtecan); and one Trop-2-targeted ADC (sacituzumab govitecan). Based on the unprecedented efficacy data demonstrated by these agents, ADCs have been incorporated as part of standard regimens for all subtypes of advanced BC, as well as for high-risk early HER2-positive BC. Despite the remarkable advances, several hurdles still remain to overcome, including the development of reliable biomarkers for patient selection, prevention, and management of potentially severe toxicities, ADC resistance mechanisms, post-ADC resistance patterns, and optimal treatment sequencing and combinations. In this review, we will summarize the currently available evidence related to the use of these agents, as well as explore the current landscape of ADC development for BC treatment.

Dataset Information

The Evolving Role of Disulfiram in Radiobiology and the Treatment of Breast Cancer.

Publications

The Evolving Role of Disulfiram in Radiobiology and the Treatment of Breast Cancer.

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