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Klotho and the Treatment of Human Malignancies

1
The Royal Marsden NHS Foundation Trust, London SW6 6JJ, UK
2
Department of Surgery and Cancer, Chelsea and Westminster Hospital, London SW10 9NH, UK
3
Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK
4
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94158, USA
5
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202-5181, USA
6
The Institute of Cancer Research, London SW3 6JB, UK
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1665; https://doi.org/10.3390/cancers12061665
Received: 26 May 2020 / Accepted: 16 June 2020 / Published: 23 June 2020
Klotho was first discovered as an anti-ageing protein linked to a number of age-related disease processes, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions. Emerging research has also demonstrated a potential therapeutic role for Klotho in cancer biology, which is perhaps unsurprising given that cancer and ageing share similar molecular hallmarks. In addition to functioning as a tumour suppressor in numerous solid tumours and haematological malignancies, Klotho represents a candidate therapeutic target for patients with these diseases, the majority of whom have limited treatment options. Here, we examine contemporary evidence evaluating the anti-neoplastic effects of Klotho and describe the modulation of downstream oncogenic signalling pathways, including Wnt/β-catenin, FGF, IGF1, PIK3K/AKT, TGFβ, and the Unfolded Protein Response. We also discuss possible approaches to developing therapeutic Klotho and consider technological advances that may facilitate the delivery of Klotho through gene therapy. View Full-Text
Keywords: Klotho; cancer; colorectal cancer Klotho; cancer; colorectal cancer
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MDPI and ACS Style

Sachdeva, A.; Gouge, J.; Kontovounisios, C.; Nikolaou, S.; Ashworth, A.; Lim, K.; Chong, I. Klotho and the Treatment of Human Malignancies. Cancers 2020, 12, 1665.

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