MGMT protein expression is a reliable predictive biomarker for temozolomide-containing chemotherapy in osteosarcoma.
Cancer Sci
; 115(10): 3394-3402, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-39080996
ABSTRACT
The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (n = 14) or as adjuvant therapy following resection of recurrent lesions (n = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, p = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, p = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Óseas
/
Metilasas de Modificación del ADN
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Biomarcadores de Tumor
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Osteosarcoma
/
Regiones Promotoras Genéticas
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Metilación de ADN
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Proteínas Supresoras de Tumor
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Enzimas Reparadoras del ADN
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Temozolomida
Idioma:
En
Revista:
Cancer Sci
/
Cancer sci
/
Cancer science (Online)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido