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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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酒精滥用药物迪苏尔菲拉姆通过p97隔离酶适配器NPL4向癌症

Zdenek Skrott1, Martin Mistrik1, Klaus Kaae Andersen2

  • 1Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

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科学领域:

  • 癌症学
  • 药理学
  • 分子生物学

背景情况:

  • 癌症发病率和耐药性增加需要新的治疗策略.
  • 药物重用提供了一种可行的方法来发现新的癌症治疗方法.
  • 迪苏尔菲拉姆 (Antabuse) 是一种抗酒精药物,已显示出临床前的抗癌作用.

研究的目的:

  • 调查dysulfiram用于癌症治疗的疗效.
  • 鉴定导致抗癌作用的迪苏尔菲拉姆活性代谢物.
  • 阐明dysulfiram抗癌作用的分子机制.

主要方法:

  • 全国范围的流行病学研究分析患者的药物使用和癌症死亡率.
  • 代谢分析以确定disufiram的活性化合物.
  • 用于确定分子点的功能和生物物理测试.

主要成果:

  • 持续使用dissulfiram与与癌症相关的死亡风险降低有关.
  • 鉴定出ditiocarb-copper复合物是dissulfiram的抗癌代谢物.
  • 迪苏尔菲拉姆向PNL4,一个p97 (VCP) 分离酶适配器,对细胞蛋白调节至关重要.

结论:

  • 迪苏尔菲拉姆是一种有前途的癌症治疗药物.
  • 滴氧碳铜复合物调解了迪苏尔菲拉姆的抗癌作用.
  • 针对NPL4提供了癌症治疗发展的新途径.