crizotinib has been researched along with Rhabdomyosarcoma* in 2 studies
2 other study(ies) available for crizotinib and Rhabdomyosarcoma
| Article | Year |
|---|---|
Lack of clinical activity with crizotinib in a patient with FUS rearranged rhabdomyosarcoma with ALK protein overexpression.
Topics: Anaplastic Lymphoma Kinase; Antineoplastic Agents; Crizotinib; DNA-Binding Proteins; Gene Rearrangement; High-Throughput Nucleotide Sequencing; Humans; Male; Positron Emission Tomography Computed Tomography; Rhabdomyosarcoma; RNA-Binding Protein FUS; Sequence Analysis, DNA; Transcription Factors; Young Adult | 2019 |
Targeting ALK in pediatric RMS does not induce antitumor activity in vivo.
The anaplastic lymphoma kinase (ALK) has been demonstrated to be a valid clinical target in diseases such as anaplastic large cell lymphoma and non-small cell lung cancer. Recent studies have indicated that ALK is overexpressed in pediatric rhabdomyosarcoma (RMS) and hence we hypothesized that this kinase may be a suitable candidate for therapeutic intervention in this tumor.. We evaluated the expression of ALK in a panel of pediatric RMS cell lines and patient-derived xenografts (PDX), and sensitivity to ALK inhibitors was assessed both in vitro and in vivo.. Essentially, all RMS lines were sensitive to crizotinib, NVP-TAE684 or LDK-378 in vitro, and molecular analyses demonstrated inhibition of RMS cell proliferation following siRNA-mediated reduction of ALK expression. However, in vivo PDX studies using ALK kinase inhibitors demonstrated no antitumor activity when used as single agents or when combined with standard of care therapy (vincristine, actinomycin D and cyclophosphamide). More alarmingly, however, crizotinib actually accelerated the growth of these tumors in vivo.. While ALK appears to be a relevant target in RMS in vitro, targeting this kinase in vivo yields no therapeutic efficacy, warranting extreme caution when considering the use of these agents in pediatric RMS patients. Topics: Anaplastic Lymphoma Kinase; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Growth Processes; Cell Line, Tumor; Crizotinib; Cyclophosphamide; Dactinomycin; Drug Interactions; Humans; Mice; Mice, Nude; Molecular Targeted Therapy; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-met; Pyrimidines; Rhabdomyosarcoma; RNA, Small Interfering; Transfection; Vincristine; Xenograft Model Antitumor Assays | 2018 |