The emerging role of selenium metabolic pathways in cancer: New therapeutic targets for cancer

Abstract

Selenium (Se) is incorporated into the body via the selenocysteine (Sec) biosynthesis pathway, which is critical in the synthesis of selenoproteins, such as glutathione peroxidases and thioredoxin reductases. Selenoproteins, which play a key role in several biological processes, including ferroptosis, drug resistance, endoplasmic reticulum stress, and epigenetic processes, are guided by Se uptake. In this review, we critically analyze the molecular mechanisms of Se metabolism and its potential as a therapeutic target for cancer. Sec insertion sequence binding protein 2 (SECISBP2), which is a positive regulator for the expression of selenoproteins, would be a novel prognostic predictor and an alternate target for cancer. We highlight strategies that attempt to develop a novel Se metabolism-based approach to uncover a new metabolic drug target for cancer therapy. Moreover, we expect extensive clinical use of SECISBP2 as a specific biomarker in cancer therapy in the near future. Of note, scientists face additional challenges in conducting successful research, including investigations on anticancer peptides to target SECISBP2 intracellular protein.

Keywords: cancer therapy; glutathione peroxidase-4; selenocysteine; selenocysteine insertion sequence binding protein 2; thioredoxin reductase 1.

Figure 1:

Graphical illustration of the role of selenium in augmenting drug resistance in cancer cells under A. in vitro and B. in vivo (via ferroptosis) conditions. (Created by Biorender.com).

Figure 2:

Diagrammatic representation of the molecular mechanisms which manifest SECISBP2 as a potential therapeutic target for cancer treatment. (Created by Biorender.com).

Figure 3:

Phage display peptide library (PDPL) - Biopanning techniques for particular target molecules (created by Biorender.com).