抗癌药物领域的新分子和新策略。

S Marchini, M D'Incalci, M Broggini
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引用次数: 16

摘要

传统的化疗主要是基于增殖细胞比非分裂细胞对抗癌药物更敏感的证据。这就是这些化合物不是肿瘤特异性的主要原因,它们的选择性通常有利于快速生长的细胞(造血细胞或肠细胞)。而不是区别对待正常细胞和肿瘤细胞之间的任何基本生物学差异。目前的关键问题是确定肿瘤细胞与正常细胞的差异,以及如何利用这些差异来设计和合成具有选择性作用机制的新药,从而提高治疗指数。这一主题和确定这些新目标的策略将在审查中详细讨论。在过去的几年里,癌细胞分子生物学知识的不断扩展,使得人们能够识别出在癌症中发生改变的不同分子途径,这些途径可能被用作潜在的治疗靶点。对于大多数先前披露的途径,开发具有相关临床影响的选择性分子一直是一个问题。针对这些特定的遗传缺陷,不同种类的分子(抗体、“反义寡核苷酸”、短肽和小分子)已经被制造出来,其中一些正在研究中。这篇综述将主要集中在三种不同类型的化合物:1 .化合物设计用于击中或抑制关键的分子靶点。2新型DNA小凹槽粘合剂。3具有新颖作用方式的海产产品。
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New molecules and strategies in the field of anticancer agents.

The conventional chemotherapy is mostly based on the evidence that proliferating cells are more sensitive to anticancer agents than non-dividing cells. This is the main reason why these compounds are not tumour specific and their selectivity is generally in favour of rapidly growing cells (haematopoietic or intestine. i.e.) rather than discriminating against any fundamental biological difference between normal and tumour cells. The critical issue is at present to identify how tumour cells differ from normal cells and how those differences can be exploited therapeutically for designing and synthesising new drugs with a selective mechanism of action and thus with an improved therapeutic index. This topic and the strategies to identify these new targets will be discussed in details in the review. The expanding knowledge on molecular biology of cancer cells has allowed in the last years the identification of different molecular pathways altered in cancer that could be exploited as potential therapeutic targets. For most of the pathways previously disclosed it has been a problem to develop selective molecules with a relevant clinic impact. To target those specific genetics defects, different kind of molecules (antibodies, "antisense oligonucleotides", short peptides and small molecules) have been made and some of them are currently under investigation. This review will be focused mainly on three different classes of compounds: I. Compounds designed to hit or inhibit crucial molecular targets. II. Novel DNA minor groove binders. III. Products of marine origin that exhibit novel mode of action.

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