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The Role of Selenium in Human Health and Disease
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The Role of Selenium in Human Health and Disease

A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 31 March 2027 | Viewed by 1940

Editor

Prof. Dr. Youcef M. Rustum

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Guest Editor
Department of Cancer Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
Interests: HIFs; TGF-b; oncogenic microRNA-210 druggable targets; mechanism-based biologic and cytotoxic therapies; COVID-19 and selenium
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Selenium (Se), an essential trace element, exerts profound pleiotropic effects on human physiology through its incorporation into selenoprotein, which serves as a key regulator of redox homeostasis, thyroid hormone metabolism, immune modulation, and DNA repair. While optimal Se status is linked to reduced risks of chronic conditions such as cardiovascular disease, neurodegeneration, and certain malignancies, both deficiency and excess manifest in distinct pathologies, including exacerbated oxidative stress. This Special Issue of International Journal of Molecular Sciences aims to elucidate the intricate molecular underpinnings of Se's dual role in health and disease, bridging nutritional science, immunology, and clinical translational research. We invite original research articles, reviews, and perspectives exploring preclinical and clinical insights into Se supplementation for cancer chemoprevention viral immunity (e.g., against SARS-CoV-2), immune modulation of targets associated with drug response and toxicity, and the potential for mechanism-based combination for cancer. We anticipate a collection that not only advances fundamental knowledge but also translates into actionable interventions for public health. By synthesizing multidisciplinary research, this issue seeks to inspire expanded research and clinical development of novel seleno-compounds for precision medicine.

Prof. Dr. Youcef M. Rustum
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • selenium
  • oxidative stress
  • immune modulation
  • cancer prevention and therapy

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Published Papers (2 papers)

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Research

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19 pages, 1117 KB  
Article
Exploration of Safety, Pharmacokinetics and Selected Pharmacodynamic Mechanisms of High-Dose Se-Methylselenocysteine, L-Selenomethionine and Selenite in a Phase Ib Trial in Cancer Patients
by Catherine M. Turnbull, Stephen O. Evans, Linda M. Peters, Renee J. Goodall, Craig K. Burns, Hugh J. B. Goodman, Natalie Briggs and Michael B. Jameson
Int. J. Mol. Sci. 2026, 27(15), 6618; https://doi.org/10.3390/ijms27156618 - 24 Jul 2026
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Abstract
High-dose selenium (Se) as selenomethionine (SLM) and sodium selenite (SS) can improve the efficacy of cancer therapies while reducing toxicity. Se-methylselenocysteine (MSC) is effective in preclinical models but has not been evaluated in cancer trials. This phase Ib randomised, double-blinded trial explored the [...] Read more.
High-dose selenium (Se) as selenomethionine (SLM) and sodium selenite (SS) can improve the efficacy of cancer therapies while reducing toxicity. Se-methylselenocysteine (MSC) is effective in preclinical models but has not been evaluated in cancer trials. This phase Ib randomised, double-blinded trial explored the safety, pharmacokinetics (PK) and selected pharmacodynamic (PD) mechanisms of MSC, SLM and SS to guide future trials. Nine participants with metastatic cancer took Se 1600 μg/day for 4 weeks, then 6400 μg/day for 4 weeks, as MSC, SLM, or SS, with safety, PK, and PD assessments at baseline then every 4 weeks for 12 weeks. No dose-limiting toxicities occurred, and all adverse events were grades 1–2, mainly gastrointestinal. Total plasma Se increased after 8 weeks to mean 27.2 μM with SLM, 4.14 μM with MSC and 3.90 μM with SS. No significant changes in DNA damage or intracellular glutathione were observed in peripheral blood mononuclear cells. Mean plasma selenoprotein P (SEPP) increased from 3.74 mg/L at baseline to 4.66 mg/L and 5.13 mg/L after 4 and 8 weeks (p = 0.136 and 0.104, respectively). More detailed evaluations of safety, PK and PD mechanisms are needed to determine a recommended Se compound and dose for larger trials in combination with cancer therapies. Full article
(This article belongs to the Special Issue The Role of Selenium in Human Health and Disease)
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Review

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22 pages, 1242 KB  
Review
Repurposing Seleno-L-Methionine as a Pleiotropic Immunomodulatory Agent to Overcome TGF-β1/HIF-Driven Immune Evasion in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Translational Therapeutic Opportunities
by Youcef M. Rustum
Int. J. Mol. Sci. 2026, 27(17), 7858; https://doi.org/10.3390/ijms27177858 - 2 Sep 2026
Viewed by 243
Abstract
Clear cell renal cell carcinoma (ccRCC) is a highly immune-evasive malignancy that exhibits limited and often transient responses to immune checkpoint inhibitors (ICIs) and remains a major challenge for emerging cellular immunotherapies, including chimeric antigen receptor (CAR)-T cells. A defining feature of ccRCC, [...] Read more.
Clear cell renal cell carcinoma (ccRCC) is a highly immune-evasive malignancy that exhibits limited and often transient responses to immune checkpoint inhibitors (ICIs) and remains a major challenge for emerging cellular immunotherapies, including chimeric antigen receptor (CAR)-T cells. A defining feature of ccRCC, largely driven by von Hippel–Lindau (VHL) deficiency, is persistent activation of the transforming growth factor-β1 (TGF-β1) and hypoxia-inducible factor (HIF) signaling network. Acting as a central immunometabolic regulatory axis, TGF-β1/HIF promotes angiogenesis, metabolic reprogramming, epigenetic dysregulation, and immune escape through coordinated induction of immunosuppressive mediators, including PD-L1, VEGF, and CTLA-4, resulting in impaired T-cell infiltration, functional exhaustion, and resistance to immunotherapy. Preclinical studies have demonstrated that pharmacologic-dose Seleno-L-methionine (SLM) and its active metabolite, methylseleninic acid (MSA), suppress TGF-β1 and both HIF-1α and HIF-2α, leading to downregulation of multiple downstream immunosuppressive pathways at pharmacologically achievable, non-toxic concentrations. In addition to enhancing the antitumor activity of chemotherapy and VEGF-targeted agents, accumulating evidence suggests that SLM exerts broad immunologic, metabolic, and epigenetic effects that may overcome key mechanisms of therapeutic resistance. This review synthesizes current mechanistic and translational evidence supporting the repurposing of SLM as a first-in-class pleiotropic immunomodulatory agent. Using ccRCC as a model of TGF-β1/HIF-driven immune resistance, we discuss how simultaneous targeting of this central regulatory axis may restore immune surveillance, improve T-cell fitness and trafficking, enhance responses to ICIs and CAR-T cell therapy, and provide a mechanistically rational strategy for the treatment of advanced solid tumors. Full article
(This article belongs to the Special Issue The Role of Selenium in Human Health and Disease)
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