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Klotho and the Treatment of Human Malignancies

The Royal Marsden NHS Foundation Trust, London SW6 6JJ, UK
Department of Surgery and Cancer, Chelsea and Westminster Hospital, London SW10 9NH, UK
Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94158, USA
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202-5181, USA
The Institute of Cancer Research, London SW3 6JB, UK
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1665;
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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