Nature Communications (Nov 2019)
The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status
- Ricky M. Trigg,
- Liam C. Lee,
- Nina Prokoph,
- Leila Jahangiri,
- C. Patrick Reynolds,
- G. A. Amos Burke,
- Nicola A. Probst,
- Miaojun Han,
- Jamie D. Matthews,
- Hong Kai Lim,
- Eleanor Manners,
- Sonia Martinez,
- Joaquin Pastor,
- Carmen Blanco-Aparicio,
- Olaf Merkel,
- Ines Garces de los Fayos Alonso,
- Petra Kodajova,
- Simone Tangermann,
- Sandra Högler,
- Ji Luo,
- Lukas Kenner,
- Suzanne D. Turner
Affiliations
- Ricky M. Trigg
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- Liam C. Lee
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- Nina Prokoph
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- Leila Jahangiri
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- C. Patrick Reynolds
- Cancer Center, Texas Tech University Health Sciences Center School of Medicine
- G. A. Amos Burke
- Department of Paediatric Oncology, Box 181, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus
- Nicola A. Probst
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- Miaojun Han
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- Jamie D. Matthews
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- Hong Kai Lim
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- Eleanor Manners
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- Sonia Martinez
- Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO)
- Joaquin Pastor
- Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO)
- Carmen Blanco-Aparicio
- Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO)
- Olaf Merkel
- Department of Experimental Pathology and Laboratory Animal Pathology, Institute of Clinical Pathology, Medical University of Vienna
- Ines Garces de los Fayos Alonso
- Department of Experimental Pathology and Laboratory Animal Pathology, Institute of Clinical Pathology, Medical University of Vienna
- Petra Kodajova
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna
- Simone Tangermann
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna
- Sandra Högler
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna
- Ji Luo
- Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health
- Lukas Kenner
- Department of Experimental Pathology and Laboratory Animal Pathology, Institute of Clinical Pathology, Medical University of Vienna
- Suzanne D. Turner
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge
- DOI
- https://doi.org/10.1038/s41467-019-13315-x
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 13
Abstract
Anaplastic lymphoma kinase (ALK) inhibitors are currently being considered in neuroblastoma (NB), but its acquired resistance is reported in non-small cell lung cancers. Here, the authors have found PIM1 overexpression decreases sensitivity to ALK inhibitors in NB and combined ALK and PIM1 inhibition enhances anti-tumour efficacy in vitro and in PDX models.
