Children's Cancer Institute Australia for Medical Research, Randwick, NSW 2031, Australia.
Nat Rev Cancer. 2010 Mar;10(3):194-204. doi: 10.1038/nrc2803. Epub 2010 Feb 11.
Microtubules are dynamic structures composed of alpha-beta-tubulin heterodimers that are essential in cell division and are important targets for cancer drugs. Mutations in beta-tubulin that affect microtubule polymer mass and/or drug binding are associated with resistance to tubulin-binding agents such as paclitaxel. The aberrant expression of specific beta-tubulin isotypes, in particular betaIII-tubulin, or of microtubule-regulating proteins is important clinically in tumour aggressiveness and resistance to chemotherapy. In addition, changes in actin regulation can also mediate resistance to tubulin-binding agents. Understanding the molecular mechanisms that mediate resistance to tubulin-binding agents will be vital to improve the efficacy of these agents.
微管是由α-β-微管蛋白异二聚体组成的动态结构，对于细胞分裂至关重要，也是癌症药物的重要靶点。β-微管中的突变会影响微管聚合质量和/或药物结合，从而导致对紫杉醇等微管结合剂的耐药性。特定β-微管亚型（尤其是βIII-微管）或微管调节蛋白的异常表达在肿瘤侵袭性和化疗耐药性方面具有重要的临床意义。此外，肌动蛋白调节的变化也可以介导对微管结合剂的耐药性。了解介导微管结合剂耐药性的分子机制对于提高这些药物的疗效至关重要。
