title: Major partial response to crizotinib, a dual MET/ALK inhibitor, in a squamous cell lung (SCC) carcinoma patient with de novo c-MET amplification in the absence of ALK rearrangement.
abstract: The initial radiotherapy of a 73 years old Caucasian male patient with advanced squamous cell lung carcinoma was terminated due to severe pericarditis. Subsequently, the tumor sample was analyzed for possible targets with comprehensive molecular diagnostics. EGFR, KRAS and PIK3CA genes were wild type, ALK and ROS1 were negative for rearrangement, but c-MET was amplified by fluorescent in situ hybridization. The kinase inhibitor crizotinib is already in clinical use for the treatment of ALK positive non-small cell lung cancers, but it is also known to be a potent c-MET inhibitor. The patient was treated with the standard dose of twice a day 250 mg crizotinib as a monotherapy. Major partial response to therapy was confirmed by chest CT and PET/CT after 8 weeks on therapy. C-MET expression is associated with poor prognosis and resistance to EGFR inhibitors. This case may indicate that c-MET tyrosine kinase inhibitors can be an effective targeted treatment option for squamous cell carcinoma patients, and future clinical trials should be expanded for this patient group as well.
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd., Budapest, Hungary.
authors.forename: Richard
authors.initials: R
authors.lastname: Schwab
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd., Budapest, Hungary; Hungarian Academy of Sciences, Pathobiochemistry Research Group, Budapest, Hungary. Electronic address: petak@kps.hu.
authors.forename: Istvan
authors.initials: I
authors.lastname: Petak
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd., Budapest, Hungary.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Kollar
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd., Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Pinter
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd., Budapest, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Varkondi
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd., Budapest, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kohanka
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd., Budapest, Hungary.
authors.forename: Helga
authors.initials: H
authors.lastname: Barti-Juhasz
authors.affiliation: Semmelweis University, Ist Department of Gynecology, Budapest, Hungary.
authors.forename: Julia
authors.initials: J
authors.lastname: Schönleber
authors.affiliation: Hungarian Academy of Sciences, Pathobiochemistry Research Group, Budapest, Hungary.
authors.forename: Diana
authors.initials: D
authors.lastname: Brauswetter
authors.affiliation: Semmelweis University, Ist Institute of Pathology and Experimental Cancer Research, Budapest, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kopper
authors.affiliation: Matrahaza Healthcare Center and University Teaching Hospital, Matrahaza, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Urban
mesh_terms: D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy; D000077547:Crizotinib; D005784:Gene Amplification; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy; D008297:Male; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D010493:Pericarditis / Q000209:etiology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D013902:Radiography, Thoracic; D011878:Radiotherapy / Q000009:adverse effects; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases
keywords: Crizotinib; Non-small cell lung cancer; Personalized medicine; Pharmacogenomics; Predictive biomarker; Receptor tyrosine kinase; Squamous cell lung cancer; Targeted therapy; c-MET