2. Academic Validation
  3. AURKB as a target in non-small cell lung cancer with acquired resistance to anti-EGFR therapy

AURKB as a target in non-small cell lung cancer with acquired resistance to anti-EGFR therapy

  • Nat Commun. 2019 Apr 18;10(1):1812. doi: 10.1038/s41467-019-09734-5.
Jordi Bertran-Alamillo 1,  Valérie Cattan 2,  Marie Schoumacher 2,  Jordi Codony-Servat 1,  Ana Giménez-Capitán 1,  Frédérique Cantero 2,  Mike Burbridge 2,  Sonia Rodríguez 1,  Cristina Teixidó 1 3,  Ruth Roman 1,  Josep Castellví 1,  Silvia García-Román 1,  Carles Codony-Servat 1,  Santiago Viteri 4,  Andrés-Felipe Cardona 5 6,  Niki Karachaliou 4,  Rafael Rosell 1 4 7 8,  Miguel-Angel Molina-Vila 9
Affiliations

Affiliations

  • 1 Laboratory of Oncology, Pangaea Oncology, Quiron Dexeus University Hospital, 08028, Barcelona, Spain.
  • 2 Institut de Recherches Internationales Servier, 92284, Suresnes, France.
  • 3 Servicio Anatomía Patológica, Hospital Clínic de Barcelona, Barcelona, 08036, Spain.
  • 4 Instituto Oncológico Dr. Rosell, Quiron-Dexeus University Hospital, 08028, Barcelona, Spain.
  • 5 Clinical and Translational Oncology Group, Institute of Oncology, Fundacion Santa Fe de Bogotá, Bogotá, 110111, Colombia.
  • 6 Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, 110111, Colombia.
  • 7 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, 08916, Badalona, Spain.
  • 8 Germans Trias i Pujol, Health Sciences Institute and Hospital, Campus Can Ruti, 08916, Badalona, Spain.
  • 9 Laboratory of Oncology, Pangaea Oncology, Quiron Dexeus University Hospital, 08028, Barcelona, Spain. mamolina@panoncology.com.
PMID: 31000705 DOI: 10.1038/s41467-019-09734-5
Abstract

Non-small cell lung Cancer (NSCLC) tumors harboring mutations in EGFR ultimately relapse to therapy with EGFR tyrosine kinase inhibitors (EGFR TKIs). Here, we show that resistant cells without the p.T790M or other acquired mutations are sensitive to the Aurora B (AURKB) inhibitors barasertib and S49076. Phospho-histone H3 (pH3), a major product of AURKB, is increased in most resistant cells and treatment with AURKB inhibitors reduces the levels of pH3, triggering G1/S arrest and polyploidy. Senescence is subsequently induced in cells with acquired mutations while, in their absence, polyploidy is followed by cell death. Finally, in NSCLC patients, pH3 levels are increased after progression on EGFR TKIs and high pH3 baseline correlates with shorter survival. Our results reveal that AURKB activation is associated with acquired resistance to EGFR TKIs, and that AURKB constitutes a potential target in NSCLC progressing to anti-EGFR therapy and not carrying resistance mutations.

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