Patterns of response to crizotinib in recurrent glioblastoma according to ALK and MET molecular profile in two patients.
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.
Neuro-Oncology, Neurosurgery Department, University Hospital - CHRU Lille, France.|Neurology, Medical Oncology Department, Oscar Lambret Center, Lille, France.|Inserm, U1192, Lille, France.
Emilie
E
Le Rhun
Neurology & Neurological Surgery, University of Washington, Fred Hutchinson Research Cancer Center, Seattle, WA 98109, USA.
Marc C
MC
Chamberlain
Inserm, U1192, Lille, France.|Neurosurgery Department, University Hospital - CHRU Lille, France.
Fahed
F
Zairi
Neuroradiology Department, University Hospital - CHRU Lille, France.
Christine
C
Delmaire
AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin; Sorbonne Universités, UPMC Univ Paris 06, UM 75.|Inserm, U 1127, CNRS, UMR 7225, ICM, F-75013 Paris, France.
Ahmed
A
Idbaih
Neuropathology Department, University Hospital - CHRU Lille, France.|Lille University, Lille, France.|UMR-S, 1172 F-59000 Lille, France.
Florence
F
Renaud
Neuropathology Department, University Hospital - CHRU Lille, France.|Lille University, Lille, France.|UMR-S, 1172 F-59000 Lille, France.
Claude Alain
CA
Maurage
Neuropathology Department, University Hospital - CHRU Lille, France.|Lille University, Lille, France.|UMR-S, 1172 F-59000 Lille, France.
Valérie
V
Grégoire
D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077547:Crizotinib; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D025521:Tumor Suppressor Proteins; D000077547:Crizotinib; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D045643:DNA Repair Enzymes
ALK; MET; MET amplification; crizotinib; glioblastoma; targeted therapy