Genes that modulate the sensitivity for anti-microtubule drug-mediated chemotherapy.
Genes that modulate the sensitivity for anti-microtubule drug-mediated chemotherapy.
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DOI：
10.2174/156800910791859434
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发表时间：
2010-09
影响因子：
3
通讯作者：
H. Yamada;C. Rao
中科院分区：
文献类型：
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作者：
H. Yamada;C. Rao
纺锤体毒药/抗微管药物是公认的化疗药物。这些药物主要针对微管和有丝分裂纺锤体，激活纺锤体组装检查点(SAC)，导致caspase介导的细胞死亡。然而，药物处理的细胞的末端表型惊人地异质性，从有丝分裂灾难到明显的衰老，表明来自各种信号通路的输入影响细胞死亡过程。近年来，研究揭示了几个调节纺锤体毒药疗效的信号通路。在这篇综述中，我们讨论了抑制或过度表达调节纺锤体毒物敏感性的基因和途径。这些基因分为(I)微管、微管相关蛋白(MAP)和肌动蛋白细胞骨架调节因子，(Ii)囊泡蛋白成分，(Iii)信号蛋白，(Iv)伴侣蛋白，(V)细胞周期调节因子，(Vi)蛋白酶体成分，(Vii)转录因子和核受体，以及()凋亡因子。这些基因产物将成为药物与纺锤体毒药结合的潜在靶点。这些基因的表达状态也可作为纺锤体毒物介导化疗的预后标志物。了解参与药物疗效的信号通路有助于合理制定协同化疗策略。
Spindle poisons/anti-microtubule drugs are established chemotherapy drugs. These drugs primarily target microtubules and mitotic spindles, activate spindle assembly checkpoint (SAC), resulting in caspase-mediated cell death. However, the terminal phenotypes of drug-treated cells are surprisingly heterogeneous ranging from mitotic catastrophe to apparent senescence, suggesting that input from a variety of signaling pathways influence the cell death process. In recent years, studies revealed several signaling pathways that modulate the efficacy of spindle poisons. In this review, we discuss the genes and pathways whose inhibition or overexpression modulates spindle poison sensitivity. These genes cluster to (i) microtubule, microtubule associating proteins (MAPS) and actin cytoskeleton regulators, (ii) the SAC components, (iii) signaling proteins, (iv) chaperones, (v) cell cycle regulators, (vi) proteasome components, (vii) transcription factors and nuclear receptors, and (viii) apoptotic factors. These gene products would be potential targets for drugs to be combined with spindle poisons. Expression status of these genes would also serve as a prognostic marker for spindle poison-mediated chemotherapy. Understanding signaling pathways involved in drug efficacy will aid to rationally develop synergistic chemotherapy strategy.