Theodosis Kalamatianos, Despoina Denekou, George Stranjalis and Evangelia Papadimitriou* Pages 209 - 223 ( 15 )
Background: Glioblastoma (GBM) is the most aggressive and common brain tumor in adults, currently lacking effective life-prolonging and recurrence-preventing therapy; median survival of GBM patients stands at only 14-16 months. Increasing lines of evidence indicate that Anaplastic lymphoma kinase (ALK), a druggable tyrosine kinase receptor over-expressed in GBM, represents a potential therapeutic target in this tumor.
Objective: An overview of the state of the art and the existing recent patents regarding potential exploitation of ALK as a therapeutic target and/or diagnostic/prognostic factor in GBM.
Method: Recent literature and patents focusing on or including ALK pre-clinical and clinical research in GBM have been identified and reviewed, and are discussed according to their potential use.
Results: Numerous recent ALK-related patents were identified. They were reviewed/analyzed in relation to previously published research and categorized based on their potential in GBM: i) diagnosis/ prognosis, ii) drug-based therapeutic targeting of ALK using a single compound or combination schemes and iii) therapeutic ALK targeting by other means, e.g. ALK vaccination.
Conclusion: ALK targeting holds promise as a novel therapeutic approach in GBM, especially in combination schemes allowing multi-target therapy. Such schemes may incorporate detection-guided therapy and utilize next generation inhibitory compounds with improved central nervous system penetration. Moreover, identification of ALK-mediated molecular pathway(s) related to GBM carcinogenesis/ pathology and putative therapy resistance is of high priority and warrants further exploitation.
Anaplastic lymphoma kinase, cancer, glioblastoma, pleiotrophin, tyrosine kinase, tyrosine kinase inhibitors.
Department of Neurosurgery, University of Athens Medical School, 10676 Athens, Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, GR26504 Patras, Department of Neurosurgery, University of Athens Medical School, 10676 Athens, Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, GR26504 Patras