Selenium compounds for cancer prevention and therapy - human clinical trial considerations

Area of Science:

• Oncology
• Nutritional Biochemistry
• Trace Element Research

Background:

• Selenium (Se) is an essential trace mineral vital for human health.
• Previous human clinical trials using seleno-methionine (SeMet) and selenized-yeast for cancer prevention in North America and Europe were unsuccessful.
• Lessons learned include testing in Se-adequate populations and the inadequacy of SeMet/selenized-yeast efficacy data.

Purpose of the Study:

• To evaluate the potential of proximal methylselenol precursors ("methyl Se") as chemopreventive and therapeutic agents against cancer.
• To discuss recommendations for future clinical studies of different Se forms for cancer therapy or chemoprevention.
• To consider Se nutrition status in populations like China where Se-deficiency persists.

Main Methods:

• Review of preclinical data on methyl-Se compounds (e.g., methylseleninic acid, Se-methylselenocysteine).
• Analysis of human clinical trial data for selenate, selenite, and selenious acid, noting safety but missing genotoxicity assessments.
• Consideration of Se-enriched food consumption patterns and nutritional Se deficiency in specific regions.

Main Results:

• Preclinical studies indicate "methyl Se" forms possess desirable attributes for targeting cancer cells and the tumor microenvironment.
• Methylseleninic acid and Se-methylselenocysteine differ in their molecular targets.
• Recent human trials with selenate, selenite, and selenious acid provided safety data but lacked genotoxicity evaluations.

Conclusions:

• The anti-oxidant hypothesis for Se in cancer prevention was likely tested inappropriately.
• "Methyl Se" compounds warrant further investigation as cancer chemopreventive and therapeutic agents.
• Future clinical trials should focus on Se forms with demonstrated preclinical efficacy and address genotoxicity, particularly in Se-deficient populations.