Lopez Jay, Ramchandani Divya, Vahdat Linda
Met Ions Life Sci. 2019 Jan 14;19. doi: 10.1515/9783110527872-018.
Copper is an essential trace element that plays a critical role in a variety of basic biological functions, and serves as a key component in a number of copper-dependent enzymes that regulate such processes as cell proliferation, angiogenesis, and motility. A growing body of preclinical work has demonstrated that copper is essential to metastatic cancer progression, and may have a role in tumor growth, epithelial-mesenchymal transition, and the formation of the tumor microenvironment and pre-metastatic niche. As a result, copper depletion has emerged as a novel therapeutic strategy in the treatment of metastatic cancer. We present a review of the physiologic role of copper with a discussion of relevant enzymes of the copper proteome in both normal tissue and in cancer. We conducted a comprehensive review of the available preclinical data of several copper chelation agents, including penicillamine, trientine, disulfiram, clioquinol, and tetrathiomolybdate (TM), across a variety of tumor types. We also present the existing early phase clinical trial data for the use of the copper chelator TM in the treatment of breast cancer and other malignancies.
铜是一种必需的微量元素，在多种基本生物学功能中发挥着关键作用，并且是许多依赖铜的酶的关键组成部分，这些酶调节细胞增殖、血管生成和运动等过程。越来越多的临床前研究表明，铜对转移性癌症进展至关重要，并且可能在肿瘤生长、上皮-间质转化以及肿瘤微环境和前转移生态位的形成中发挥作用。因此，铜耗竭已成为治疗转移性癌症的一种新的治疗策略。我们对铜的生理作用进行综述，并讨论正常组织和癌症中铜蛋白质组的相关酶。我们对几种铜螯合剂（包括青霉胺、曲恩汀、双硫仑、氯碘喹啉和四硫钼酸盐（TM））在多种肿瘤类型中的现有临床前数据进行了全面综述。我们还展示了铜螯合剂TM用于治疗乳腺癌和其他恶性肿瘤的现有早期临床试验数据。
