Producción CyT
Congreso
Autoría
Senovieski, Matías Luis
;
Clement, Florencia
;
Barrios, Evelin
;
MARTIN, AYELEN
;
Pennisi, Patricia
Fecha
2025
Editorial y Lugar de Edición
Fundación Revista Medicina
Resumen
Información suministrada por el agente en
SIGEVA
Pediatric central nervous system tumors—especially gliomas—are the most common solid tumors in children. Previously we found that in pediatric gliomas, nuclear localization of IGF1R is significantly associated with high-grade tumors and increased mortality risk. Current standard treatment for high-grade gliomas includes surgical resection followed by radiotherapy and Temozolomide (TMZ)chemotherapy, though optimal regimens remain to be defined. We aimed to characterize the in vitro a...
Pediatric central nervous system tumors—especially gliomas—are the most common solid tumors in children. Previously we found that in pediatric gliomas, nuclear localization of IGF1R is significantly associated with high-grade tumors and increased mortality risk. Current standard treatment for high-grade gliomas includes surgical resection followed by radiotherapy and Temozolomide (TMZ)chemotherapy, though optimal regimens remain to be defined. We aimed to characterize the in vitro and in vivo response of glioma cells to IGF1R inhibition using OSI906, alone or in combination with high or low TMZ doses. We used U87MG glioblastoma cells expressing wild-type IGF1R (WtU87) or a mutant form that cannot translocate to the nucleus (MutU87). We performed in vitro(Wt U87-, MutU87- derived spheroids) and in vivo (sc injection, nude male mice) studies to test OSI906, TMZ or the combination of both drugs, added to the culturing media (40 or 100 nM TMZ,5uM OSI) or orally administered to the mice. In 3D spheroid cultures, both lines were sensitive to TMZ (p<0.03),but MutU87spheroids did not respond to OSI906. The combination of OSI906and TMZ did not enhance MutU87 spheroid volume reduction. In vivo, WtU87-derived tumors grew faster and larger than MutU87tumors (p<0.05), and only WtU87 tumors showed sensitivity toOSI906, especially when combined with low-dose TMZ (p<0.02).These findings indicate that nuclear IGF1R enhances sensitivity toIGF1R-targeted therapy, suggesting that in pediatric gliomas with nuclear IGF1R, treatment with inhibitors like OSI906 may allow for reduced TMZ dosing and potentially avoid radiotherapy in young children
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Palabras Clave
Pediatric GliomasIGF1ROSI906