Anaplastic Lymphoma Kinase in Glioblastoma: Detection/Diagnostic Methods and Therapeutic Options.

ABSTRACT

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.