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Resistance To Taxanes

  • Chapter
Cancer Drug Resistance

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Resistance to two taxanes, paclitaxel and docetaxel, is frequently observed in cancer patients and limits successful therapy. In experimental systems, resistance to paclitaxel and docetaxel are mediated by alterations in tubulin (the primary site of action of taxanes), proteins that interact with microtubules, energy-dependent efflux pumps, apoptotic proteins, and signal transduction pathways. Clinical correlations with some of these alterations exist, but have not been fully elucidated. Strategies to overcome or circumvent resistance to paclitaxel or docetaxel include inhibition of efflux pumps (which have largely proven to be unsuccessful), the use of novel taxanes or other chemically distinct classes of polymerizing agents that do not interact with drug efflux pumps (currently in clinical trials), and regulation of apoptotic or signal transduction pathways that would restore sensitivity to taxanes. Understanding the basis of resistance at the clinical level is likely to be difficult and complex, but holds the promise of providing a therapeutic opportunity specific to taxane-resistant cancer cells.

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  1. Cancer Therapeutics Research, Johnson & Johnson, Raritan, NJ

    Lee M. Greenberger PhD

  2. Oncology Research, Wyeth Research, Pearl River, NY

    Deepak Sampath PhD

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  1. Genzyme Corporation, Framingham, MA

    Beverly A. Teicher PhD

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Greenberger, L.M., Sampath, D. (2006). Resistance To Taxanes. In: Teicher, B.A. (eds) Cancer Drug Resistance. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-035-5_18

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