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NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer

Nature Reviews Urology volume 11, pages 499–507 (2014)Cite this article

Subjects

Key Points

  • NUMB is a complex protein with multiple cellular functions

  • NUMB negatively regulates the NOTCH signalling pathway

  • The NUMB–NOTCH interaction regulates cell fate in prostate tumours

  • Targeting NUMB has potential to control prostate tumorigenesis

  • NUMB profiling could assist the identification of patients with prostate cancer who are likely to benefit from NOTCH-inhibition strategies

Abstract

Prostate cancer is among the most prevalent life-threatening cancers diagnosed in the male population today. Various methods have been exploited in an attempt to treat this disease but these treatments, alongside preventative tactics, have been insufficient to control mortality rates and have usually resulted in detrimental adverse events. An opportunity to devise more-specific and potentially more-effective approaches for the eradication of prostate tumours can be found by targeting specific biological pathways. NUMB (protein numb homologue), a key regulator of cell fate, represents an attractive, actionable target in prostate cancer. NUMB participates in the observed deregulation of NOTCH (neurogenic locus notch homologue protein) signalling in prostate tumours, and the NUMB–NOTCH interaction regulates cell fate. NUMB has potential both as a target for control of prostate tumorigenesis and as a biomarker for identification of patients with prostate cancer who are likely to benefit from NOTCH inhibition.

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Figure 1: The multiple functions of NUMB.
Figure 2: Inhibition of the NOTCH pathway by NUMB.

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Acknowledgements

We would like to acknowledge support from the Irish Cancer Society (grant code PCA12MAR). Victoria Anastasia Belle is a Mount Sinai International Exchange Program minority student participant. Her work was supported in part by grant MD001452 from the National Center on Minority Health and Health Disparities of the National Institutes of Health.

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Authors and Affiliations

  1. Division of International Health, Mount Sinai School of Medicine, New York, 10029, NY, USA

    Victoria Anastasia Belle

  2. Radiation and Urologic Oncology, Applied Radiation Therapy Trinity and Prostate Molecular Oncology Research Group, Trinity College Dublin, Trinity Centre for Health Sciences, James's Street, Dublin, 8, Ireland

    Niamh McDermott, Armelle Meunier & Laure Marignol

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V.A.B. and L.M. researched the data for the article, discussed the content and wrote the article. All authors contributed to review and editing of the manuscript before submission.

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Correspondence to Laure Marignol.

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Belle, V., McDermott, N., Meunier, A. et al. NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer. Nat Rev Urol 11, 499–507 (2014). https://doi.org/10.1038/nrurol.2014.195

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