Microtubules and resistance to tubulin-binding agents.
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.
Kavallaris
Maria
M
Children's Cancer Institute Australia for Medical Research, Randwick, NSW 2031, Australia. mkavallaris@ccia.unsw.edu.au
D000818:Animals; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000627:therapeutic use; D011485:Protein Binding; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000627:therapeutic use*
D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel