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The ALK receptor in sympathetic neuron development and neuroblastoma

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Abstract

The ALK gene encodes a tyrosine kinase receptor characterized by an expression pattern mainly restricted to the developing central and peripheral nervous systems. In 2008, the discovery of ALK activating mutations in neuroblastoma, a tumor of the sympathetic nervous system, represented a breakthrough in the understanding of the pathogenesis of this pediatric cancer and established mutated ALK as a tractable therapeutic target for precision medicine. Subsequent studies addressed the identity of ALK ligands, as well as its physiological function in the sympathoadrenal lineage, its role in neuroblastoma development and the signaling pathways triggered by mutated ALK. This review focuses on these different aspects of the ALK biology and summarizes the various therapeutic strategies relying on ALK inhibition in neuroblastoma, either as monotherapies or combinatory treatments.

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Acknowledgements

The U830 Inserm laboratory is supported by grants from the Ligue Nationale contre le Cancer (Equipe labellisée), the Institut National du Cancer (PRT-K 14061), the Association Hubert Gouin « Enfance et Cancer », Les Bagouz à Manon, les amis de Claire, la Fédération Enfants et Santé et la Société Française de Lutte contre les Cancers et les Leucémies de l’Enfant et l’Adolescent. L. L.-D. was the recipient of a fellowship of the Fondation pour la Recherche Médicale (FDT20140930966). H.R. is supported by the Mayent-Rothschild program from Institut Curie and the Wilhelm-Sander-Stiftung.

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  1. Lucille Lopez-Delisle

    Present address: Laboratory of Developmental Genomics, EPFL SV ISREC UPDUB, SV 2843, CH-1015, Lausanne, Switzerland

Authors and Affiliations

  1. Institut Curie, PSL Research University, Inserm U830, Equipe Labellisée Ligue contre le Cancer, F-75005, Paris, France

    Isabelle Janoueix-Lerosey, Lucille Lopez-Delisle & Olivier Delattre

  2. SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, F-75005, Paris, France

    Isabelle Janoueix-Lerosey & Olivier Delattre

  3. Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590, Frankfurt am Main, Germany

    Hermann Rohrer

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Janoueix-Lerosey, I., Lopez-Delisle, L., Delattre, O. et al. The ALK receptor in sympathetic neuron development and neuroblastoma. Cell Tissue Res 372, 325–337 (2018). https://doi.org/10.1007/s00441-017-2784-8

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