Editing Paclitaxel (section)

==Mechanism of action==
[[File:Tubulin&paclitaxel-2HXF.png|thumb|Complex of α, β tubulin subunits and paclitaxel. Paclitaxel is shown as yellow stick.]]
Paclitaxel is one of several [[cytoskeletal drugs]] that target [[tubulin]]. Paclitaxel-treated cells have defects in [[mitotic spindle]] assembly, [[chromosome segregation]], and [[cell division]]. Unlike other tubulin-targeting drugs, such as [[colchicine]], that inhibit [[microtubule]] assembly, paclitaxel stabilizes the microtubule polymer and protects it from disassembly. Chromosomes are thus unable to achieve a [[metaphase]] spindle configuration.  This blocks the progression of [[mitosis]] and prolonged activation of the [[mitotic checkpoint]] triggers [[apoptosis]] or reversion to the [[G0 phase|G0-phase]] of the cell cycle without cell division.<ref>{{cite journal | vauthors = Bharadwaj R, Yu H | title = The spindle checkpoint, aneuploidy, and cancer | journal = Oncogene | volume = 23 | issue = 11 | pages = 2016–2027 | date = March 2004 | pmid = 15021889 | doi = 10.1038/sj.onc.1207374 | s2cid = 11114877 | doi-access =  }}</ref><ref>{{cite journal | vauthors = Brito DA, Yang Z, Rieder CL | title = Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied | journal = The Journal of Cell Biology | volume = 182 | issue = 4 | pages = 623–629 | date = August 2008 | pmid = 18710927 | pmc = 2518701 | doi = 10.1083/jcb.200805072 }}</ref>

The ability of paclitaxel to inhibit spindle function is generally attributed to its suppression of microtubule dynamics,<ref>{{cite journal | vauthors = Jordan MA, Wilson L | title = Microtubules as a target for anticancer drugs | journal = Nature Reviews. Cancer | volume = 4 | issue = 4 | pages = 253–265 | date = April 2004 | pmid = 15057285 | doi = 10.1038/nrc1317 | s2cid = 10228718 }}</ref> but other studies have demonstrated that suppression of dynamics occurs at concentrations lower than those needed to block mitosis. At the higher therapeutic concentrations, paclitaxel appears to suppress microtubule detachment from [[centrosome]]s, a process normally activated during mitosis.<ref>{{cite journal | vauthors = Ganguly A, Yang H, Cabral F | title = Paclitaxel-dependent cell lines reveal a novel drug activity | journal = Molecular Cancer Therapeutics | volume = 9 | issue = 11 | pages = 2914–2923 | date = November 2010 | pmid = 20978163 | pmc = 2978777 | doi = 10.1158/1535-7163.MCT-10-0552 }}</ref> Paclitaxel binds to the beta-tubulin subunits of microtubules.<ref>{{cite journal | vauthors = Löwe J, Li H, Downing KH, Nogales E | title = Refined structure of alpha beta-tubulin at 3.5 A resolution | journal = Journal of Molecular Biology | volume = 313 | issue = 5 | pages = 1045–1057 | date = November 2001 | pmid = 11700061 | doi = 10.1006/jmbi.2001.5077 | url = https://zenodo.org/record/1229896 | access-date = 29 August 2020 | archive-date = 22 January 2021 | archive-url = https://web.archive.org/web/20210122161041/https://zenodo.org/record/1229896 | url-status = live }}</ref>