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Polo-like kinases and acute leukemia

Oncogene volume 38, pages 1–16 (2019)Cite this article

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Abstract

Acute leukemia is a common malignancy among children and adults worldwide and many patients suffer from chronic health issues using current therapeutic approaches. Therefore, there is a great need for the development of novel and more specific therapies with fewer side effects. The family of Polo-like kinases (Plks) is a group of five serine/threonine kinases that play an important role in cell cycle regulation and are critical targets for therapeutic invention. Plk1 and Plk4 are novel targets for cancer therapy as leukemic cells often express higher levels than normal cells. In contrast, Plk2 and Plk3 are considered to be tumor suppressors. Several small molecule inhibitors have been developed for targeting Plk1 inhibition. Despite reaching phase III clinical trials, one of the ATP-competitive Plk1 inhibitor, volasertib, did not induce an objective clinical response and even caused lethal side effects in some patients. In order to improve the specificity of the Plk1 inhibitors and reduce off-target side effects, novel RNA interference (RNAi)-based therapies have been developed. In this review, we summarize the mechanisms of action of the Plk family members in acute leukemia, describe preclinical studies and clinical trials involving Plk-targeting drugs and discuss novel approaches in Plk targeting.

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Acknowledgements

This study was supported by the Swedish Foundation for Strategic Research (C.P.A.) and the Swedish Childhood Cancer Foundation (C.P.A.).

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Authors and Affiliations

  1. Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden

    Oksana Goroshchuk, Iryna Kolosenko, Linda Vidarsdottir, Alireza Azimi & Caroline Palm-Apergi

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  1. Oksana Goroshchuk
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  2. Iryna Kolosenko
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  3. Linda Vidarsdottir
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  4. Alireza Azimi
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  5. Caroline Palm-Apergi
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Corresponding author

Correspondence to Caroline Palm-Apergi.

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Goroshchuk, O., Kolosenko, I., Vidarsdottir, L. et al. Polo-like kinases and acute leukemia. Oncogene 38, 1–16 (2019). https://doi.org/10.1038/s41388-018-0443-5

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  • DOI: https://doi.org/10.1038/s41388-018-0443-5

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