Department of Life Sciences, University of Trieste, Italy.
Curr Drug Metab. 2013 Jun;14(5):565-82. doi: 10.2174/13892002113149990010.
Aptamer researches applied to the treatment of human cancers have increased since their discovery in 1990. This is due to different factors including: 1) the technical possibility to select, by SELEX-based procedures, specific aptamers targeting virtually any given molecule, 2) the aptamer favorable bio-activity in vivo, 3) the low production costs and 4) the ease synthesis and storage for the marketing. In the field of cancer treatments, aptamers have been studied as tumor-specific agents driving drugs into cancer cells; additionally they have been used as anti-neoplastic agents, able to inhibit tumor cell growth and dissemination when administered alone or in combination with conventional anti-neoplastic drugs. Aptamers are gaining an increased interest for pharmaceutical companies and some of them are under clinical evaluation trials. In this review we update the findings about the use of aptamers as "escort" molecules able to drive drugs into the cells and as antineoplastic drugs. Current anti-neoplastic treatments suffer from the intrinsic toxicity related to the un-specific targeting of both normal and tumorigenic proliferating cells. The aptamers could be useful to improve: 1) the selective targeting of molecules essential for the viability and expansion of tumor cells and/or the selective driving of chemotherapies into tumor cells, thus resulting in higher effectiveness and lower systemic side-effects compared to conventional anti-neoplastic drugs alone and 2) to improve the therapeutic index of currently used chemotherapies. Even if some problems related to the in vivo stability and pharmacokinetic/dynamics of aptamers remain to be improved, their potential use in the treatment of different human cancers is getting closer and closer to a practical therapeutic use.
自 1990 年发现以来,适体研究在人类癌症治疗中的应用有所增加。这是由于以下几个因素:1)通过基于 SELEX 的程序选择针对几乎任何给定分子的特异性适体的技术可能性,2)适体在体内的良好生物活性,3)低生产成本和 4)易于合成和储存以用于市场营销。在癌症治疗领域,适体已被研究为肿瘤特异性药物,将药物靶向癌细胞;此外,它们已被用作抗肿瘤药物,当单独使用或与常规抗肿瘤药物联合使用时,能够抑制肿瘤细胞生长和扩散。适体越来越受到制药公司的关注,其中一些正在进行临床试验评估。在这篇综述中,我们更新了关于适体作为“护航”分子将药物输送到细胞内以及作为抗肿瘤药物的使用的发现。当前的抗肿瘤治疗方法存在与正常和肿瘤增殖细胞的非特异性靶向相关的固有毒性。适体可以用于提高:1)对肿瘤细胞存活和扩张所必需的分子的选择性靶向,和/或对化疗药物进入肿瘤细胞的选择性驱动,从而与单独使用常规抗肿瘤药物相比,提高了有效性和降低了全身副作用,2)提高目前使用的化疗药物的治疗指数。尽管与适体体内稳定性和药代动力学/动力学相关的一些问题仍有待改善,但它们在治疗不同人类癌症中的潜在用途越来越接近实际治疗用途。