The RANK–RANKL axis: an opportunity for drug repurposing in cancer?

• S. Peters ^[1] ; P. Clézardin ^[4] ; I. Márquez-Rodas ^[2] ; D. Niepel ^[5] ; C. Gedye ^[3]
  1. [1] University Hospital of Lausanne

     University Hospital of Lausanne

     Lausana, Suiza

     
  2. [2] Hospital General Universitario Gregorio Marañón

     Hospital General Universitario Gregorio Marañón

     Madrid, España

     
  3. [3] Calvary Mater Newcastle Hospital

     Calvary Mater Newcastle Hospital

     Australia

     
  4. [4] INSERM, Institut national de la santé et de la recherche médicale UMR 1033, Universite Claude Bernard Lyon-1, Francia
  5. [5] Amgen Switzerland AG, Suiza

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 21, Nº. 8 (August), 2019, págs. 977-991
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Drug repurposing offers advantages over traditional drug development in terms of cost, speed and improved patient outcomes. The receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) inhibitor denosumab is approved for the prevention of skeletal-related events in patients with advanced malignancies involving bone, including solid tumours and multiple myeloma. Following improved understanding of the role of RANK/RANKL in cancer biology, denosumab has already been repurposed as a treatment for giant cell tumour of bone. Here, we review the role of RANK/RANKL in tumourigenesis, including effects on tumour initiation, progression and metastasis and consider the impact of RANK/RANKL on tumour immunology and immune evasion. Finally, we look briefly at ongoing trials and future opportunities for therapeutic synergy when combining denosumab with anti-cancer agents such as immune checkpoint inhibitors.