Mary Babb Randolph Cancer Center, West Virginia University Schools of Pharmacy and Medicine, Morgantown, WV, USA.
Breast Cancer. 2011 Apr;18(2):103-19. doi: 10.1007/s12282-010-0224-7. Epub 2010 Sep 23.
Manifestations of non-equilibrium polarity, random transgressions, and catastrophes are not conditions usually associated with a sense of normalcy. Yet these disquieting features distinguish a utilitarian behavior known as dynamic instability, the signature characteristic of the microtubule. Long known to be a tumor target, disruption of this fragile attribute is associated with some of the most effective agents used to treat breast cancer today. Although the biology of the microtubule is under intense investigation much still remains unknown. As such, our understanding of regulatory molecules and resistance mechanisms are still rudimentary, further compromising our ability to develop novel therapeutic strategies to improve microtubule inhibitors. This review focuses on several classes of anti-microtubule agents and their effects on the functional dynamics of the targeted polymer. The primary objective is to critically examine the molecular mechanisms that contribute to tumor cell death, tumor-resistance, and incident neurotoxicity.
非平衡极性、随机越界和灾难的表现形式通常与正常状态无关。然而,这些令人不安的特征区分了一种被称为动态不稳定性的功利性行为,这是微管的特征。长期以来,微管一直被认为是肿瘤的靶点,破坏这种脆弱的属性与目前用于治疗乳腺癌的一些最有效药物有关。尽管微管的生物学正在受到深入研究,但仍有许多未知。因此,我们对调节分子和耐药机制的理解仍然很初级,这进一步削弱了我们开发新的治疗策略来改善微管抑制剂的能力。这篇综述集中讨论了几类抗微管药物及其对靶向聚合物功能动力学的影响。主要目的是批判性地检查导致肿瘤细胞死亡、肿瘤耐药性和神经毒性的分子机制。