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Microtubules, Drug Resistance, and Tumorigenesis

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Cytoskeleton and Human Disease

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Abstract

Microtubules are highly dynamic structures that comprise a- and b-tubulin heterodimers which are essential in mitosis. These features make microtubules an important target for many natural and synthetic anticancer drugs. Mutations in b-tubulin that affect microtubule polymer levels or drug binding are associated with resistance to tubulin-binding agents such as paclitaxel. Moreover, aberrant expression of specific b-tubulin isotypes, namely bIII-tubulin as well as microtubule-binding proteins are now recognized as clinically important determinants in tumor aggressiveness and resistance to chemotherapy. More recently, it has been suggested that b-tubulins may also be linked to the tumorigenic phenotype of certain cancers such as non-small-cell lung cancer. Understanding the mechanisms whereby b-tubulins exert their effect on drug resistance and tumorigenesis are critical to the identification of novel drug targets and improvements in current therapies to increase the long-term survival of cancer patients.

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Acknowledgments

We would like to thank all the researchers who have contributed to our understanding of microtubules, drug resistance, and cancer, and due to space limits we regret that we were not able to cite all the important contributions to the field. Joshua McCarroll and Maria Kavallaris are supported by grants from the National Health and Medical Research Council (NHMRC), Cancer Council New South Wales (MK), Cure Cancer Australia Foundation Grant (JM), Balnaves Young Researcher Award (JM), Cancer Institute New South Wales Early Career Development Fellowship (JM), and an NHMRC Senior Research Fellowship (MK).

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Authors and Affiliations

  1. Children’s Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, 2052, Sydney, NSW, Australia

    Joshua A. McCarroll & Maria Kavallaris Ph.D.

  2. Australian Centre for Nanomedicine, Faculty of Engineering, University of New South Wales, Sydney, NSW, Australia

    Joshua A. McCarroll & Maria Kavallaris Ph.D.

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  1. Joshua A. McCarroll
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  2. Maria Kavallaris Ph.D.
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Correspondence to Maria Kavallaris Ph.D. .

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  1. Australia for Medical Research, Iron Metabolism Program, Children's Cancer Institute, Randwick, New South Wales, Australia

    Maria Kavallaris

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McCarroll, J.A., Kavallaris, M. (2012). Microtubules, Drug Resistance, and Tumorigenesis. In: Kavallaris, M. (eds) Cytoskeleton and Human Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-788-0_12

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