Sachdeva, AishaniGouge, JeromeKontovounisios, ChristosNikolaou, StellaAshworth, AlanLim, KennethChong, Irene2021-02-012021-02-012020-06-23Sachdeva, A., Gouge, J., Kontovounisios, C., Nikolaou, S., Ashworth, A., Lim, K., & Chong, I. (2020). Klotho and the Treatment of Human Malignancies. Cancers, 12(6), 1665. https://doi.org/10.3390/cancers12061665https://hdl.handle.net/1805/25107Klotho 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.en-USAttribution 4.0 InternationalKlothocancercolorectal cancerArticle