Microtubules are required for many aspects of cellular function, including mitosis. This has made them an attractive target for the development of cancer drugs.
Although drugs that target tubulin and microtubules are widely used in the clinic, resistance — both inherent and acquired — is common.
Understanding the function of tubulin in cancer development and resistance to tubulin-binding agents (TBAs) might aid the development of more effective drugs.
The expression of different β-tubulin isotypes is disrupted in cancer cells, and understanding how this contributes to disease progression and drug resistance is essential. Overexpression or aberrant expression of βIII-tubulin can affect the response of tumour cells to TBAs. The mechanisms that underlie this are currently unclear. Understanding the role of the other β-tubulin isotypes in cancer development is also at an early stage.
Proteins that regulate microtubules, such as microtubule-associated proteins and stathmin, are also implicated in drug resistance. How, mechanistically, these proteins influence resistance to TBAs is under investigation.
Changes to the actin cytoskeleton also contribute to drug resistance but how such changes relate to the microtubule system needs further clarification.
Microtubules are dynamic structures composed of α–β-tubulin heterodimers that are essential in cell division and are important targets for cancer drugs. Mutations in β-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 β-tubulin isotypes, in particular βIII-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.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs
Cell Death & Disease Open Access 27 January 2023
An EHMT2/NFYA-ALDH2 signaling axis modulates the RAF pathway to regulate paclitaxel resistance in lung cancer
Molecular Cancer Open Access 27 April 2022
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Verhey, K. J. & Gaertig, J. The tubulin code. Cell Cycle 6, 2152–2160 (2007).
Pepperkok, R., Bre, M. H., Davoust, J. & Kreis, T. E. Microtubules are stabilized in confluent epithelial cells but not in fibroblasts. J. Cell Biol. 111, 3003–3012 (1990).
Saxton, W. M. et al. Tubulin dynamics in cultured mammalian cells. J. Cell Biol. 99, 2175–2186 (1984).
Rusan, N. M., Fagerstrom, C. J., Yvon, A. M. & Wadsworth, P. Cell cycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-α tubulin. Mol. Biol. Cell 12, 971–980 (2001).
Zhai, Y., Kronebusch, P. J., Simon, P. M. & Borisy, G. G. Microtubule dynamics at the G2/M transition: abrupt breakdown of cytoplasmic microtubules at nuclear envelope breakdown and implications for spindle morphogenesis. J. Cell Biol. 135, 201–214 (1996).
Jordan, M. A. & Wilson, L. Microtubules as a target for anticancer drugs. Nature Rev. Cancer 4, 253–265 (2004).
Kavallaris, M., Don, S. & Verrills, N. M. in Microtubule Targets in Cancer Therapy (ed. Fojo, A.) 84–106 (Humana, Totowa, New Jersey, 2008).
Perez, E. A. Microtubule inhibitors: differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance. Mol. Cancer Ther. 8, 2086–2095 (2009).
Downing, K. H. Structural basis for the interaction of tubulin with proteins and drugs that affect microtubule dynamics. Annu. Rev. Cell Dev. Biol. 16, 89–111 (2000).
Nettles, J. H. et al. The binding mode of epothilone A on α, β-tubulin by electron crystallography. Science 305, 866–869 (2004). The first high-resolution crystal structure that described binding sites for epothilone A on α–β-tubulin.
Rieder, C. L. & Maiato, H. Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Dev. Cell 7, 637–651 (2004).
Gascoigne, K. E. & Taylor, S. S. How do anti-mitotic drugs kill cancer cells? J. Cell Sci. 122, 2579–2585 (2009).
Gascoigne, K. E. & Taylor, S. S. Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell 14, 111–122 (2008). The first comprehensive study showing that there is cell-to-cell variation and intra-cell variation in response to anti-mitotic drugs.
Shi, J., Orth, J. D. & Mitchison, T. Cell type variation in responses to antimitotic drugs that target microtubules and kinesin-5. Cancer Res. 68, 3269–3276 (2008).
Steen, J. A. et al. Different phosphorylation states of the anaphase promoting complex in response to antimitotic drugs: a quantitative proteomic analysis. Proc. Natl Acad. Sci. USA 105, 6069–6074 (2008).
Brito, D. A., Yang, Z. & Rieder, C. L. Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied. J. Cell Biol. 182, 623–629 (2008).
Brito, D. A. & Rieder, C. L. The ability to survive mitosis in the presence of microtubule poisons differs significantly between human nontransformed (RPE-1) and cancer (U2OS, HeLa) cells. Cell Motil. Cytoskeleton 66, 437–447 (2009).
Brito, D. A. & Rieder, C. L. Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr. Biol. 16, 1194–1200 (2006).
Vakoc, B. J. et al. Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nature Med. 15, 1219–1223 (2009).
Luduena, R. F. Multiple forms of tubulin: different gene products and covalent modifications. Int. Rev. Cytol. 178, 207–275 (1998).
Verdier-Pinard, P. et al. Tubulin proteomics: towards breaking the code. Anal. Biochem. 384, 197–206 (2009). A detailed review of how proteomics is being used to identify tubulin isotypes and post-translational modifications of isotypes.
Hammond, J. W., Cai, D. & Verhey, K. J. Tubulin modifications and their cellular functions. Curr. Opin. Cell Biol. 20, 71–76 (2008).
Freedman, H., Huzil, J. T., Luchko, T., Luduena, R. F. & Tuszynski, J. A. Identification and characterization of an intermediate taxol binding site within microtubule nanopores and a mechanism for tubulin isotype binding selectivity. J. Chem. Inf. Model 49, 424–436 (2009).
Westermann, S. & Weber, K. Post-translational modifications regulate microtubule function. Nature Rev. Mol. Cell Biol. 4, 938–947 (2003).
O'Brate, A. & Giannakakou, P. The importance of p53 location: nuclear or cytoplasmic zip code? Drug Resist. Updat. 6, 313–322 (2003).
Bhalla, K. N. Microtubule-targeted anticancer agents and apoptosis. Oncogene 22, 9075–9086 (2003).
Mollinedo, F. & Gajate, C. Microtubules, microtubule-interfering agents and apoptosis. Apoptosis 8, 413–450 (2003).
Esteve, M. A., Carre, M. & Braguer, D. Microtubules in apoptosis induction: are they necessary? Curr. Cancer Drug Targets 7, 713–729 (2007).
Li, R., Moudgil, T., Ross, H. J. & Hu, H. M. Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim. Cell Death Differ. 12, 292–303 (2005).
Ferrandina, G. et al. Class III β-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin. Cancer Res. 12, 2774–2779 (2006).
Kavallaris, M. et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific β-tubulin isotypes. J. Clin. Invest. 100, 1282–1293 (1997). The first report describing alterations in β-tubulin isotype expression in taxol-resistant clinical samples.
Martello, L. A. et al. Elevated levels of microtubule destabilizing factors in a taxol-resistant/dependent A549 cell line with an α-tubulin mutation. Cancer Res. 63, 1207–1213 (2003).
Don, S. et al. Neuronal-associated microtubule proteins class III β-tubulin and MAP2c in neuroblastoma: role in resistance to microtubule-targeted drugs. Mol. Cancer Ther. 3, 1137–1146 (2004).
Rouzier, R. et al. Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc. Natl Acad. Sci. USA 102, 8315–8320 (2005).
Tommasi, S. et al. Cytoskeleton and paclitaxel sensitivity in breast cancer: the role of β-tubulins. Int. J. Cancer 120, 2078–2085 (2007).
Seve, P. & Dumontet, C. Is class III β-tubulin a predictive factor in patients receiving tubulin-binding agents? Lancet Oncol. 9, 168–175 (2008).
Pasquier, E. & Kavallaris, M. Microtubules: a dynamic target in cancer therapy. IUBMB Life 60, 165–170 (2008).
Berrieman, H. K., Lind, M. J. & Cawkwell, L. Do β-tubulin mutations have a role in resistance to chemotherapy? Lancet Oncol. 5, 158–164 (2004).
Hodgkinson, J. E., Clark, H. J., Kaplan, R. M., Lake, S. L. & Matthews, J. B. The role of polymorphisms at β tubulin isotype 1 codons 167 and 200 in benzimidazole resistance in cyathostomins. Int. J. Parasitol. 38, 1149–1160 (2008).
Sale, S. et al. Conservation of the class I β-tubulin gene in human populations and lack of mutations in lung cancers and paclitaxel-resistant ovarian cancers. Mol. Cancer Ther. 1, 215–225 (2002).
Katsetos, C. D., Herman, M. M. & Mork, S. J. Class III β-tubulin in human development and cancer. Cell. Motil. Cytoskeleton 55, 77–96 (2003).
Katsetos, C. D., Draberova, E., Legido, A., Dumontet, C. & Draber, P. Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I. class III β-tubulin. J. Cell Physiol. 221, 505–513 (2009). A detailed review of βIII-tubulin expression in glioblastoma.
Lee, K. M. et al. Class III β-tubulin, a marker of resistance to paclitaxel, is overexpressed in pancreatic ductal adenocarcinoma and intraepithelial neoplasia. Histopathology 51, 539–546 (2007).
Hari, M., Yang, H., Zeng, C., Canizales, M. & Cabral, F. Expression of class III β-tubulin reduces microtubule assembly and confers resistance to paclitaxel. Cell Motil. Cytoskeleton 56, 45–56 (2003).
Kamath, K., Wilson, L., Cabral, F. & Jordan, M. A. βIII-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability. J. Biol. Chem. 280, 12902–12907 (2005).
Kavallaris, M., Burkhart, C. A. & Horwitz, S. B. Antisense oligonucleotides to class III β-tubulin sensitize drug-resistant cells to taxol. Br. J. Cancer 80, 1020–1025 (1999).
Liu, B., Staren, E., Iwamura, T., Appert, H. & Howard, J. Taxotere resistance in SUIT: taxotere resistance in pancreatic carcinoma cell line SUIT 2 and its sublines. World J. Gastroenterol. 7, 855–859 (2001).
Gan, P. P., Pasquier, E. & Kavallaris, M. Class III β-tubulin mediates sensitivity to chemotherapeutic drugs in non small cell lung cancer. Cancer Res. 67, 9356–9363 (2007).
Raspaglio, G. et al. Hypoxia induces class III β-tubulin gene expression by HIF-1α binding to its 3′ flanking region. Gene 409, 100–108 (2008). The demonstration that hypoxia can induce βIII-tubulin expression in some cell types.
Cicchillitti, L. et al. Proteomic characterization of cytoskeletal and mitochondrial class III β-tubulin. Mol. Cancer Ther. 7, 2070–2079 (2008).
Dennis, K., Uittenbogaard, M., Chiaramello, A. & Moody, S. A. Cloning and characterisation of the 5′-flanking region of the rat neuron-specific class III β-tubulin gene. Gene 294, 269–277 (2002).
Seve, P. et al. Expression of class III β-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy. Clin. Cancer Res. 11, 5481–5486 (2005). This paper provided strong evidence for a role for βIII-tubulin in clinical outcome in NSCLC.
Seve, P. et al. Class III β-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel. Mol. Cancer Ther. 4, 2001–2007 (2005).
Portyanko, A., Kovalev, P., Gorgun, J. & Cherstvoy, E. βIII-tubulin at the invasive margin of colorectal cancer: possible link to invasion. Virchows Arch. 454, 541–548 (2009).
Cochrane, D. R., Spoelstra, N. S., Howe, E. N., Nordeen, S. K. & Richer, J. K. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol. Cancer Ther. 8, 1055–1066 (2009).
Aoki, D. et al. Favourable prognosis with modified dosing of docetaxel and cisplatin in Japanese patients with ovarian cancer. Anticancer Res. 29, 561–566 (2009).
Ferrandina, G. et al. Expression of class III β tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome. Gynecol. Oncol. 104, 326–330 (2007).
Caracciolo, V. et al. Differential expression and cellular distribution of γ-tubulin and βIII-tubulin in medulloblastomas and human medulloblastoma cell lines. J. Cell Physiol. (in the press).
Mhaidat, N. M., Thorne, R. F., de Bock, C. E., Zhang, X. D. & Hersey, P. Melanoma cell sensitivity to docetaxel-induced apoptosis is determined by class III β-tubulin levels. FEBS Lett. 582, 267–272 (2008).
Akasaka, K. et al. Loss of class III β-tubulin induced by histone deacetylation is associated with chemosensitivity to paclitaxel in malignant melanoma cells. J. Invest. Dermatol. 129, 1516–1526 (2009).
Bernard-Marty, C. et al. Microtubule-associated parameters as predictive markers of docetaxel activity in advanced breast cancer patients: results of a pilot study. Clin. Breast Cancer 3, 341–345 (2002).
Dozier, J. H. et al. β class II tubulin predominates in normal and tumor breast tissues. Breast Cancer Res. 5, R157–R169 (2003).
Cucchiarelli, V. et al. β-tubulin isotype classes II and V expression patterns in nonsmall cell lung carcinomas. Cell. Motil. Cytoskeleton 65, 675–685 (2008).
Blade, K., Menick, D. R. & Cabral, F. Overexpression of class I, II or IVb β-tubulin isotypes in CHO cells is insufficient to confer resistance to paclitaxel. J. Cell Sci. 112, 2213–2221 (1999). A detailed functional study demonstrating that exogenous expression of βI-, βII- or βIVb-tubulin does not influence sensitivity to paclitaxel.
Burkhart, C. A., Kavallaris, M. & Band Horwitz, S. The role of β-tubulin isotypes in resistance to antimitotic drugs. Biochim. Biophys. Acta 1471, O1–O9 (2001).
Gan, P. P. & Kavallaris, M. Tubulin-targeted drug action: functional significance of class II and class IVb β-tubulin in vinca alkaloid sensitivity. Cancer Res. 68, 9817–9824 (2008). The first functional evidence that βII- and βIVb-tubulin mediate sensitivity to vinca alkaloids.
Mozzetti, S. et al. Molecular mechanisms of patupilone resistance. Cancer Res. 68, 10197–10204 (2008).
Bhattacharya, R. & Cabral, F. A ubiquitous β-tubulin disrupts microtubule assembly and inhibits cell proliferation. Mol. Biol. Cell 15, 3123–3131 (2004).
Thomas, E. et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer. J. Clin. Oncol. 25, 3399–3406 (2007).
Thomas, E. S. et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J. Clin. Oncol. 25, 5210–5217 (2007).
Ten Bokkel Huinink, W. W. et al. Safety and efficacy of patupilone in patients with advanced ovarian, primary fallopian, or primary peritoneal cancer: a Phase I, open-label, dose-escalation study. J. Clin. Oncol. 27, 3097–3103 (2009).
Sabbatini, P. & Spriggs, D. R. Epothilones: better or more of the same? J. Clin. Oncol. 27, 3079–3081 (2009).
Vansteenkiste, J. et al. Phase II clinical trial of the epothilone B analog, ixabepilone, in patients with non small-cell lung cancer whose tumors have failed first-line platinum-based chemotherapy. J. Clin. Oncol. 25, 3448–3455 (2007).
Dumontet, C., Jordan, M. A. & Lee, F. F. Ixabepilone: targeting βIII-tubulin expression in taxane-resistant malignancies. Mol. Cancer Ther. 8, 17–25 (2009).
Magnani, M. et al. The βI/βIII-tubulin isoforms and their complexes with antimitotic agents. Docking and molecular dynamics studies. FEBS J. 273, 3301–3310 (2006).
Tanaka, S. et al. Tau expression and efficacy of paclitaxel treatment in metastatic breast cancer. Cancer Chemother. Pharmacol. 64, 341–346 (2009).
Ferlini, C. et al. Looking at drug resistance mechanisms for microtubule interacting drugs: does TUBB3 work? Curr. Cancer Drug Targets. 7, 704–712 (2007).
Baselga, J. et al. Phase II genomics study of ixabepilone as neoadjuvant treatment for breast cancer. J. Clin. Oncol. 27, 526–534 (2009).
Murphy, M., Hinman, A. & Levine, A. J. Wild-type p53 negatively regulates the expression of a microtubule-associated protein. Genes Dev. 10, 2971–2980 (1996).
Zhang, C. C. et al. DNA damage increases sensitivity to vinca alkaloids and decreases sensitivity to taxanes through p53-dependent repression of microtubule-associated protein 4. Cancer Res. 59, 3663–3670 (1999).
Bash-Babula, J. et al. A Phase I/pilot study of sequential doxorubicin/vinorelbine: effects on p53 and microtubule-associated protein 4. Clin. Cancer Res. 8, 1057–1064 (2002).
Gigant, B. et al. Structural basis for the regulation of tubulin by vinblastine. Nature 435, 519–522 (2005).
Rana, S., Maples, P. B., Senzer, N. & Nemunaitis, J. Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev. Anticancer Ther. 8, 1461–1470 (2008).
McGrogan, B. T., Gilmartin, B., Carney, D. N. & McCann, A. Taxanes, microtubules and chemoresistant breast cancer. Biochim. Biophys. Acta 1785, 96–132 (2008).
Belletti, B. et al. Stathmin activity influences sarcoma cell shape, motility, and metastatic potential. Mol. Biol. Cell 19, 2003–2013 (2008).
Alli, E., Yang, J. M., Ford, J. M. & Hait, W. N. Reversal of stathmin-mediated resistance to paclitaxel and vinblastine in human breast carcinoma cells. Mol. Pharmacol. 71, 1233–1240 (2007).
Su, D. et al. Stathmin and tubulin expression and survival of ovarian cancer patients receiving platinum treatment with and without paclitaxel. Cancer 115, 2453–2463 (2009).
Devred, F. et al. Stathmin/Op18 is a novel mediator of vinblastine activity. FEBS Lett. 582, 2484–2488 (2008).
Verrills, N. M., Walsh, B. J., Cobon, G. S., Hains, P. G. & Kavallaris, M. Proteome analysis of vinca alkaloid response and resistance in acute lymphoblastic leukemia reveals novel cytoskeletal alterations. J. Biol. Chem. 278, 45082–45093 (2003).
Rodriguez, O. C. et al. Conserved microtubule–actin interactions in cell movement and morphogenesis. Nature Cell Biol. 5, 599–609 (2003).
Hall, A. The cytoskeleton and cancer. Cancer Metastasis Rev. 28, 5–14 (2009).
Verrills, N. M. & Kavallaris, M. Drug resistance mechanisms in cancer cells: a proteomics perspective. Curr. Opin. Mol. Ther. 5, 258–265 (2003).
Verrills, N. M. et al. Proteomic analysis reveals a novel role for the actin cytoskeleton in vincristine resistant childhood leukemia — an in vivo study. Proteomics 6, 1681–1694 (2006).
Verrills, N. M. et al. Alterations in γ-actin and tubulin-targeted drug resistance in childhood leukemia. J. Natl Cancer Inst. 98, 1363–1374 (2006). The finding that a component of the actin cytoskeleton, γ-actin, can mediate sensitivity to TBAs.
Dan, S. et al. An integrated database of chemosensitivity to 55 anticancer drugs and gene expression profiles of 39 human cancer cell lines. Cancer Res. 62, 1139–1147 (2002).
Bernard, O. Lim kinases, regulators of actin dynamics. Int. J. Biochem. Cell Biol. 39, 1071–1076 (2007).
Acevedo, K., Moussi, N., Li, R., Soo, P. & Bernard, O. LIM kinase 2 is widely expressed in all tissues. J. Histochem. Cytochem. 54, 487–501 (2006).
Sumi, T., Hashigasako, A., Matsumoto, K. & Nakamura, T. Different activity regulation and subcellular localization of LIMK1 and LIMK2 during cell cycle transition. Exp. Cell Res. 312, 1021–1030 (2006).
Po'uha, S. T., Shum, M. S., Goebel, A., Bernard, O. & Kavallaris, M. LIM-kinase 2, a regulator of actin dynamics, is involved in mitotic spindle integrity and sensitivity to microtubule-destabilizing drugs. Oncogene 29, 597–607 (2010).
Ahmed, A. A. et al. The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel. Cancer Cell 12, 514–527 (2007).
Meads, M. B., Gatenby, R. A. & Dalton, W. S. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nature Rev. Cancer 9, 665–674 (2009).
Teicher, B. A. Acute and chronic in vivo therapeutic resistance. Biochem. Pharmacol. 77, 1665–1673 (2009).
Cabral, F. Factors determining cellular mechanisms of resistance to antimitotic drugs. Drug Resist. Updat. 4, 3–8 (2001).
Schiff, P. B., Horwitz, S. B. Taxol stabilizes microtubules in mouse fibroblast cells. Proc. Natl Acad. Sci. USA 77, 1561–1565 (1980).
Hunt, J. T. Discovery of ixabepilone. Mol. Cancer Ther. 8, 275–281 (2009).
Howard, J. & Hyman, A. A. Dynamics and mechanics of the microtubule plus end. Nature 422, 753–758 (2003).
Heald, R. & Nogales, E. Microtubule dynamics. J. Cell Sci. 115, 3–4 (2002).
Rubin, C. I. & Atweh, G. F. The role of stathmin in the regulation of the cell cycle. J. Cell Biochem. 93, 242–250 (2004).
Verrills, N. M. & Kavallaris, M. Improving the targeting of tubulin-binding agents: lessons from drug resistance studies. Curr. Pharm. Des. 11, 1719–1733 (2005).
Mozzetti, S. et al. Class III β-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin. Cancer Res. 11, 298–305 (2005).
Ohishi, Y. et al. Expression of β-tubulin isotypes in human primary ovarian carcinoma. Gynecol. Oncol. 105, 586–592 (2007).
Hasegawa, S. et al. Prediction of response to docetaxel by quantitative analysis of class I and III β-tubulin isotype mRNA expression in human breast cancers. Clin. Cancer Res. 9, 2992–2997 (2003).
Paradiso, A. et al. Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer. Ann. Oncol. 16, iv14–iv19 (2005).
Rosell, R. et al. Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer. Oncogene 22, 3548–3553 (2003).
Koh, Y. et al. Class III β-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma. Ann. Oncol. 20, 1414–1419 (2009).
Urano, N. et al. Clinical significance of class III β-tubulin expression and its predictive value for resistance to docetaxel-based chemotherapy in gastric cancer. Int. J. Oncol. 28, 375–381 (2006).
The author was supported by a Senior Research Fellowship, grants from the National Health and Medical Research Council and a grant from the Cancer Council New South Wales. I thank E. Pasquier and J. Mccarroll for their critical reading of and suggestions for the review.
The author declares no competing financial interests.
National Cancer Institute Drug Dictionary
This organelle is also called the 'microtubule-organizing centre' and is located near the nucleus in the cytoplasm.
- Mitotic asters
Microtubules that radiate from the mitotic spindle poles to the cell cortex. Asters are involved in the positioning and alignment of the spindle poles during cell division.
A complicated protein assembly that links the specialized areas of condensed chromosomes (centromeres) to the microtubule-based mitotic spindle.
- Intravital microscopy
This technique uses a sophisticated research microscope that allows the microcirculation and complex biological interactions in organs to be directly visualized in real time in anaesthetized animals.
A consensus DNA site recognized by the transcription factor MYC.
A speckled staining pattern in cells that is often made up of proteins or protein aggregates.
Rights and permissions
About this article
Cite this article
Kavallaris, M. Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer 10, 194–204 (2010). https://doi.org/10.1038/nrc2803
This article is cited by
TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs
Cell Death & Disease (2023)
Xanthatin and 8-epi-xanthatin as new potential colchicine binding site inhibitors: a computational study
Journal of Molecular Modeling (2023)
An EHMT2/NFYA-ALDH2 signaling axis modulates the RAF pathway to regulate paclitaxel resistance in lung cancer
Molecular Cancer (2022)
Polarity protein Par3 sensitizes breast cancer to paclitaxel by promoting cell cycle arrest
Breast Cancer Research and Treatment (2022)
Design, synthesis, characterization and cytotoxic activity of new ortho-hydroxy and indole-chalcone derivatives against breast cancer cells (MCF-7)
Medicinal Chemistry Research (2022)