Ganguly Anutosh, Cabral Fernando
Department of Integrative Biology and Pharmacology, University of Texas Medical School, 6431 Fannin Street, houston, TX 77030, USA.
Biochim Biophys Acta. 2011 Dec;1816(2):164-71. doi: 10.1016/j.bbcan.2011.06.001. Epub 2011 Jun 29.
Mechanisms to explain tumor cell resistance to drugs that target the microtubule cytoskeleton have relied on the assumption that the drugs act either to suppress microtubule dynamics or to perturb the balance between assembled and nonassembled tubulin. Recently, however, it was found that these drugs also alter the stability of microtubule attachment to centrosomes, and do so at the same concentrations that are needed to inhibit cell division. Based on this new information, a new model is presented that explains resistance resulting from a variety of molecular changes that have been reported in the literature. The improved understanding of drug action and resistance has important implications for chemotherapy with these agents.
药物要么抑制微管动力学，要么扰乱组装态与非组装态微管蛋白之间的平衡。然而，最近发现这些药物还会改变微管与中心体附着的稳定性，而且在抑制细胞分裂所需的相同浓度下就能做到这一点。基于这一新信息，本文提出了一个新模型，该模型解释了文献中报道的各种分子变化所导致的耐药性。对药物作用和耐药性的深入理解对这些药物的化疗具有重要意义。
