title: Cancer chemoprevention research with selenium in the post-SELECT era: Promises and challenges.
abstract: The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of nonsmall cell lung cancer (NSCLC) in North America lead to rejection of SeMet/Se-yeast for cancer prevention in Se-adequate populations. We identify 2 major lessons from the outcomes of these trials: 1) the antioxidant hypothesis was tested in wrong subjects or patient populations, and 2) the selection of Se agents was not supported by cell culture and preclinical animal efficacy data as is common in drug development. We propose that next-generation forms of Se (next-gen Se), such as methylselenol precursors, offer biologically appropriate approaches for cancer chemoprevention but these are faced with formidable challenges. Solid mechanism-based preclinical efficacy assessments and comprehensive safety studies with next-gen Se will be essential to revitalize the idea of cancer chemoprevention with Se in the post-SELECT era. We advocate smaller mechanism-driven Phase I/II trials with these next-gen Se to guide and justify future decisions for definitive Phase III chemoprevention efficacy trials.
authors.affiliation: a Department of Biomedical Sciences , School of Pharmacy, Texas Tech University Health Sciences Center , Amarillo , Texas , USA.
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lü
authors.affiliation: a Department of Biomedical Sciences , School of Pharmacy, Texas Tech University Health Sciences Center , Amarillo , Texas , USA.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a Department of Biomedical Sciences , School of Pharmacy, Texas Tech University Health Sciences Center , Amarillo , Texas , USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: b Hormel Institute, University of Minnesota , Austin , Minnesota , USA.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: c Department of Pathology , University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA and Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Bezmiâlem Vakif University , Istanbul , Turkey.|d Department of Pharmaceutical Toxicology , Faculty of Pharmacy, Bezmiâlem Vakif University , Istanbul , Turkey.
authors.forename: Nur
authors.initials: N
authors.lastname: Özten
authors.affiliation: c Department of Pathology , University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA and Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Bezmiâlem Vakif University , Istanbul , Turkey.
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Bosland
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D018890:Chemoprevention; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D040901:Proteomics; D018036:Selenium Compounds / Q000378:metabolism / Q000627:therapeutic use* / Q000633:toxicity; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D018036:Selenium Compounds; D014810:Vitamin E; D013880:Thioredoxin-Disulfide Reductase