Analyses of FGFR3 and PIK3CA mutations in neuroblastomas and the effects of the corresponding inhibitors on neuroblastoma cell lines.
Int J Oncol
; 55(6): 1372-1384, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31638167
ABSTRACT
Fibroblast growth factor receptor (FGFR)3 and phosphatidylinositol4,5bisphosphate 3kinase, catalytic subunit alpha (PIK3CA) mutations are found in various types of cancer, such as urinary bladder cancer, human papillomaviruspositive tonsillar and base of the tongue squamous cell carcinoma, breast cancer and some childhood sarcomas. Several drugs can target these genes, some of which have been used for the treatment of urinary bladder cancer. Much less is known about childhood cancer. For this reason, the present study investigated the presence of such mutations in neuroblastomas (NBs) and tested NB cell lines for sensitivity to FGFR and phosphoinositide 3kinase (PI3K) inhibitors. In total, 29 NBs were examined for the presence of the three most common FGFR3 and PIK3CA mutations using a competitive allelespecific TaqMan PCR (CASTPCR). Furthermore, the SKNAS, SKNBE(2)C, SKNDZ, SKNFI and SKNSH NB cell lines (where SKNDZ had a deletion of PIK3C2G, none had FGFR mutations according to the Cancer Program's Dependency Map, but some were chemoresistant), were tested for sensitivity to FGFR (AZD4547) and PI3K (BEZ235 and BKM120) inhibitors by viability, cytotoxicity, apoptosis and proliferation assays. CASTPCR detected one FGFR3 mutation in 1/29 NBs. Following treatment with FGFR and PI3K inhibitors, a decrease in viability and proliferation was observed in the majority, but not all, the cell lines. Following combination treatment with both drugs, the sensitivity of all cell lines was increased. On the whole, the findings of this study demonstrate that FGFR3 and PIK3CA mutations are uncommon in patients with NB. However, certain NB cell lines are rather sensitive to both FGFR and PI3K inhibitors alone, and even more so when the different drugs are used in combination.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Receptor Tipo 3 de Fator de Crescimento de Fibroblastos
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Classe I de Fosfatidilinositol 3-Quinases
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Inibidores de Fosfoinositídeo-3 Quinase
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Neuroblastoma
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article