title: Selenium protects against toxicity induced by anticancer drugs and augments antitumor activity: a highly selective, new, and novel approach for the treatment of solid tumors.
abstract: Limited therapeutic selectivity and tumor resistance are major obstacles to current chemotherapy. The development of new therapeutic modalities for solid tumor remains a challenge. The use of selenium, 5-methylselenocysteine (MSC), or seleno-L-methionine (SLM) as selective modulators of anticancer drugs is novel and has not been previously investigated. Selenium deficiency is associated with an increased risk of cancer and cancer death. Although low-dose selenium supplementation has been investigated in a large randomized prevention trial, its potential in chemotherapy toxicity prevention and enhancement of antitumor activity of anticancer drugs has not been evaluated. An ideal biomodulator of anticancer drugs would allow escalation of drug dose with the hope of enhancing antitumor activity and possibly reversing drug resistance. Results from this laboratory have demonstrated that MSC and SLM are highly effective modulators of irinotecan cure rates in de novo sensitive and resistant human tumor xenografts. Studies in mice have documented that the minimum effective dose of MSC when combined with irinotecan is 0.01 mg daily. The optimal schedule is to administer MSC orally for 7 days before and concurrently with irinotecan. The observed effects were not drug-specific, as similar results were obtained with taxanes, platinum agents, 5-fluorouracil, and anthracyclines; nor were they species-specific, as selective effects were obtained in mice and rats and are currently being confirmed in ongoing clinical trials.
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Marwan
authors.initials: M
authors.lastname: Fakih
authors.forename: Shousong
authors.initials: S
authors.lastname: Cao
authors.forename: Farukh A
authors.initials: FA
authors.lastname: Durrani
authors.forename: Youcef M
authors.initials: YM
authors.lastname: Rustum
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000633:toxicity; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017279:Selenocysteine / Q000031:analogs & derivatives; D012645:Selenomethionine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016566:Organoselenium Compounds; D017279:Selenocysteine; D000077146:Irinotecan; D012645:Selenomethionine; D003545:Cysteine; C002979:selenomethylselenocysteine; D002166:Camptothecin