Abstract
Two patients with an unmethylated MGMT promoter and IDH1 (R132H) wild-type recurrent glioblastoma were treated with crizotinib. Prolonged stabilization of the disease (17 months) was achieved in the first case. Interestingly, anaplastic lymphoma kinase (ALK) expression and c-MET protein overexpression was observed. Conversely, no response to crizotinib was obtained in the second case with MET protein overexpression and c-MET amplification but no ALK expression or ALK gene amplification. These case studies suggest that novel targeted ALK inhibitors may provide relevant clinical benefit in selected cases in which driver mutations are demonstrable.
Keywords:
ALK; MET; MET amplification; crizotinib; glioblastoma; targeted therapy.
MeSH terms
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Adult
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Anaplastic Lymphoma Kinase
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Antineoplastic Agents / therapeutic use*
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Brain / drug effects
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Brain / pathology
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Brain Neoplasms / drug therapy*
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism*
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Brain Neoplasms / pathology
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Crizotinib
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DNA Modification Methylases / genetics
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DNA Repair Enzymes / genetics
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Female
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Follow-Up Studies
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Glioblastoma / drug therapy*
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Glioblastoma / genetics
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Glioblastoma / metabolism*
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Glioblastoma / pathology
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Humans
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Immunohistochemistry
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Isocitrate Dehydrogenase / genetics
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Magnetic Resonance Imaging
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Male
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Middle Aged
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins c-met / metabolism*
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Pyrazoles / therapeutic use*
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Pyridines / therapeutic use*
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Receptor Protein-Tyrosine Kinases / metabolism*
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Tumor Suppressor Proteins / genetics
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Pyrazoles
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Pyridines
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Tumor Suppressor Proteins
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Crizotinib
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Isocitrate Dehydrogenase
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IDH1 protein, human
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DNA Modification Methylases
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MGMT protein, human
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ALK protein, human
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Anaplastic Lymphoma Kinase
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MET protein, human
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Proto-Oncogene Proteins c-met
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Receptor Protein-Tyrosine Kinases
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DNA Repair Enzymes