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苯氧二醇:癌症单一疗法以及与化疗药物联合使用的药理学及临床经验

Phenoxodiol: pharmacology and clinical experience in cancer monotherapy and in combination with chemotherapeutic drugs.

作者信息

Silasi Dan-Arin, Alvero Ayesha B, Rutherford Thomas J, Brown David, Mor Gil

机构信息

Yale University School of Medicine, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology & Reproductive Sciences, New Haven, CT 06520, USA.

出版信息

Expert Opin Pharmacother. 2009 Apr;10(6):1059-67. doi: 10.1517/14656560902837980.

Abstract

BACKGROUND

Phenoxodiol is a synthetic derivative of the naturally occurring plant isoflavone genistein. The observation that an inverse relationship exists between dietary intake of isoflavones and cancer incidence has led to the evaluation of these compounds in cancer therapy.

OBJECTIVE

This article reviews the mechanisms of action of phenoxodiol and the completed and ongoing clinical studies evaluating this drug.

RESULTS/CONCLUSIONS: By altering the chemical structure of genistein, the new compound phenoxodiol showed increased anticancer activity without any increase in toxicity. In addition to its direct cytotoxic activity against different cancers, phenoxodiol sensitizes chemoresistant ovarian cancer cells to platinum and taxane drugs, as well as gemcitabine and topotecan. The US Food and Drug Administration has granted 'fast track' status to the development of phenoxodiol as chemosensitizer for platinum and taxane drugs used in the treatment of recurrent ovarian cancer.

摘要

背景

苯氧二醇是天然存在的植物异黄酮染料木黄酮的合成衍生物。异黄酮的饮食摄入量与癌症发病率之间存在负相关关系,这一观察结果促使人们对这些化合物在癌症治疗中的作用进行评估。

目的

本文综述了苯氧二醇的作用机制以及评估该药物的已完成和正在进行的临床研究。

结果/结论:通过改变染料木黄酮的化学结构,新化合物苯氧二醇显示出增强的抗癌活性,且毒性未增加。除了对不同癌症具有直接细胞毒性活性外,苯氧二醇还能使耐化疗的卵巢癌细胞对铂类和紫杉烷类药物以及吉西他滨和拓扑替康敏感。美国食品药品监督管理局已授予苯氧二醇“快速通道”地位,用于开发作为治疗复发性卵巢癌的铂类和紫杉烷类药物的化学增敏剂。

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