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Kinesin motor proteins as targets for cancer therapy

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Abstract

The process of mitosis is a validated point of intervention in cancer therapy and a variety of anti-mitotic drugs are successfully being used in the clinic. To date, all approved antimitotics target the spindle microtubules, thus interfering with spindle dynamics, leading to mitotic arrest and apoptosis. While effective, these drugs are also associated with a variety of side effects, including neurotoxicity. In recent years, mitotic kinesins have attracted significant attention in the search for novel, alternative mitotic drug targets. Due to their specific function in mitosis, targeting these proteins creates an opportunity for the development of more selective antimitotics with an improved side effect profile. In addition, kinesin inhibitors may overcome resistance to microtubule targeting drugs. Drug discovery efforts in this area have initially focused on the plus-end directed kinesin spindle protein (KSP) and a variety of compounds are currently undergoing clinical testing.

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Acknowledgments

We thank Daniel Russell, Victor Sandor and Louise Grochow for critical review of the manuscript.

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Authors and Affiliations

  1. Cancer Bioscience, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA, 02451, USA

    Dennis Huszar

  2. Cancer and Infection Research Area, AstraZeneca, Mereside, Alderley Park, Macclesfield, SK10 4TG, UK

    Maria-Elena Theoclitou

  3. Clinical Research, Oncology, AstraZeneca, 1800 Concord Pike, Wilmington, DE, 19850, USA

    Jeffrey Skolnik

  4. MedImmune, Inc., One MedImmune Way, Gaithersburg, MD, 20878, USA

    Ronald Herbst

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  1. Dennis Huszar
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  2. Maria-Elena Theoclitou
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  4. Ronald Herbst
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Correspondence to Ronald Herbst.

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Huszar, D., Theoclitou, ME., Skolnik, J. et al. Kinesin motor proteins as targets for cancer therapy. Cancer Metastasis Rev 28, 197–208 (2009). https://doi.org/10.1007/s10555-009-9185-8

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