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Mechanisms of Taxol resistance related to microtubules

Oncogene volume 22, pages 7280–7295 (2003)Cite this article

Abstract

Since its approval by the FDA in 1992 for the treatment of ovarian cancer, the use of Taxol has dramatically increased. Although treatment with Taxol has led to improvement in the duration and quality of life for some cancer patients, the majority eventually develop progressive disease after initially responding to Taxol treatment. Drug resistance represents a major obstacle to improving the overall response and survival of cancer patients. This review focuses on mechanisms of Taxol resistance that occur directly at the microtubule, such as mutations, tubulin isotype selection and post-translational modifications, and also at the level of regulatory proteins. A review of tubulin structure, microtubule dynamics, the mechanism of action of Taxol and its binding site on the microtubule are included, so that the reader can evaluate Taxol resistance in context.

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Acknowledgements

We thank our many colleagues, who have worked with us over the years, for their interest and contributions to studies on drug resistance. This work was supported in part by USPHS Grants CA 39821 (SBH), CA 77263 (SBH) and the National Foundation for Cancer Research (SBH), AI49749 (GAO) and Department of Defence Breast Cancer Research Program DAMD17-01-0123 (GAO). H.M.D. was supported by postdoctoral fellowship 99-3054 from the Susan B. Komen foundation.

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  1. Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, NY, USA

    George A Orr, Pascal Verdier-Pinard, Hayley McDaid & Susan Band Horwitz

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Orr, G., Verdier-Pinard, P., McDaid, H. et al. Mechanisms of Taxol resistance related to microtubules. Oncogene 22, 7280–7295 (2003). https://doi.org/10.1038/sj.onc.1206934

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