crizotinib and Sarcoma--Ewing
crizotinib has been researched along with Sarcoma--Ewing* in 2 studies
Reviews
1 review(s) available for crizotinib and Sarcoma--Ewing
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[Molecular biology of sarcoma and therapeutic choices].
Soft tissue sarcomas (STS) are a set of very heterogeneous tumors with numerous histological categories. The development of the molecular biology allowed identifying recurring molecular anomalies in certain subgroups of sarcomas, being able to represent diagnostic, prognosis and therapeutic tools. The molecular classification of STS includes until today 5 main groups of abnormalities: sarcomas with "simple genomic profile" showing reciprocal (1) chromosomal translocations, (2) activating mutation, (3) inhibitive mutation or (4) simple amplification; (5) sarcomas with "complex genomic profile" can include several tens of molecular abnormalities. The development of new-targeted therapies is based on the identification of a target, specific of a tumors subgroup and involved in carcinogenesis mechanisms and/or tumoral growth. Then, the aim of clinical research is to establish the proof of the concept through clinical trials, demonstrating the benefit brought to the patient and ending in the marketing of the drug. This proof of the concept was clearly established for imatinib, sunitinib and regorafenib in gastrointestinal stromal tumors, for imatinib in dermatofibrosarcoma protuberans and pigmented vilo-nodular synovitis, for denosumab in giant cell tumors of the bone, ending in the authorization to use these new therapies in these indications. It is in progress and promising for anti-IGF-1R in Ewing sarcomas, for crizotinib in myofibroblastic inflammatory tumors, for mTOR inhibitor in PEComas... The role of molecular abnormalities identified in the mechanisms of tumoral progress for sarcomas and their potential therapeutic impact will be detailed. Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Benzamides; Bone Neoplasms; Crizotinib; Denosumab; Dermatofibrosarcoma; Gastrointestinal Stromal Tumors; Gene Amplification; Gene Deletion; Giant Cell Tumor of Bone; Humans; Imatinib Mesylate; Indoles; Molecular Targeted Therapy; Phenylurea Compounds; Piperazines; Point Mutation; Prognosis; Pyrazoles; Pyridines; Pyrimidines; Pyrroles; Sarcoma; Sarcoma, Ewing; Sunitinib; Synovitis, Pigmented Villonodular; Translocation, Genetic | 2015 |
Other Studies
1 other study(ies) available for crizotinib and Sarcoma--Ewing
Article | Year |
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Expression and clinical relevance of MET and ALK in Ewing sarcomas.
Because novel therapeutic options are limited in Ewing sarcomas (ES), we investigated the expression, genetic aberrations and clinical relevance of MET and anaplastic lymphoma kinase (ALK) in ES and determined the relevance of targeting these receptors. MET and ALK protein expression was determined immunohistochemically in 31 (50 samples) and 36 (59 samples) ES patients, respectively. Samples included primary tumors, postchemotherapy resections, metastases and relapses. MET and ALK RTK domains were sequenced in respectively 33 and 32 tumors. Five ES cell lines were treated in vitro with the MET/ALK-inhibitor crizotinib, the ALK-inhibitor NVP-TAE684 or the MET-inhibitor cabozantinib and analyzed by MTT assays. Modest to high MET and ALK expression was detected in the majority of ES (86 and 69%, respectively). ALK expression was significantly lower in postchemotherapy resections compared to paired untreated primary tumors (p = 0.031, z = -2.310, n = 11). In primary tumors (n = 20), membranous MET expression significantly correlated with a poor overall survival (OS) (60 vs. 197 months, p = 0.014). There was a trend toward a poor event-free survival (67 vs. 111 months, p = 0.078) and OS (88 vs. 128 months, p = 0.074) in patients with highest ALK levels (n = 29). ALK or MET RTK domain aberrations were demonstrated in 5/32 (16%) and 3/33 (9%) tumors, respectively. Crizotinib (IC50 1.22-3.59 μmol/L), NVP-TAE684 (IC50 0.15-0.79 μmol/L) and cabozantinib (IC50 2.69-8.27 μmol/L) affected ES cell viability in vitro. Altogether, our data suggest that MET and ALK are potential novel therapeutic targets in ES and targeting these receptors may be of great interest to rationally design future studies in ES. Topics: Adolescent; Adult; Anaplastic Lymphoma Kinase; Anilides; Child; Child, Preschool; Chromosome Aberrations; Crizotinib; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Inhibitory Concentration 50; Male; Middle Aged; Neoplasm Metastasis; Proto-Oncogene Proteins c-met; Pyrazoles; Pyridines; Pyrimidines; Receptor Protein-Tyrosine Kinases; Recurrence; Sarcoma, Ewing; Tetrazolium Salts; Thiazoles; Treatment Outcome; Young Adult | 2013 |