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.
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.
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DOI：
10.3816/ccc.2005.n.026
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Rustum, Youcef M
中科院分区：
文献类型：
--
作者：
Fakih, Marwan;Cao, Shousong;Rustum, Youcef M
有限的治疗选择性和肿瘤耐药性是目前化疗的主要障碍。开发新的实体瘤治疗模式仍然是一个挑战。硒、5-甲基硒代半胱氨酸（MSC）或硒代-L-甲硫氨酸（SLM）作为抗癌药物的选择性调节剂的用途是新颖的，并且先前未被研究。硒缺乏与癌症和癌症死亡的风险增加有关。虽然在一项大型随机预防试验中研究了低剂量硒补充剂，但尚未评估其在预防化疗毒性和增强抗癌药物抗肿瘤活性方面的潜力。理想的抗癌药物生物调节剂将允许药物剂量的增加，希望增强抗肿瘤活性并可能逆转耐药性。该实验室的结果表明，MSC和SLM是从头敏感和耐药人肿瘤异种移植物中伊立替康治愈率的高效调节剂。在小鼠中的研究已经证明，当与伊立替康组合时，MSC的最小有效剂量为每天0.01 mg。最佳方案是在伊立替康之前和同时口服MSC 7天。观察到的效应不是药物特异性的，因为紫杉烷类、铂类药物、5-氟尿嘧啶和蒽环类药物获得了类似的结果;它们也不是种属特异性的，因为在小鼠和大鼠中获得了选择性效应，目前正在进行的临床试验中得到证实。
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.