Antiangiogenic therapy with bevacizumab in recurrent malignant gliomas: analysis of the response and core pathway aberrations

摘要: BACKGROUND Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown promising activity in recurrent malignant gliomas. We reported the treatment response for combination of bevacizumab and chemotherapy series six patients with glioma investigated molecular alterations cancer pathways using surgical biopsies from these patients. METHODS Standard therapy primary resection followed by adjuvant chemoradiotherapy had failed all Bevacizumab was administered at dose 10 mg/kg every 2 weeks. Concomitantly, four received temozolomide (50 mgxm(-2)xd(-1)), one patient irinotecan (125 mg/m(2) weeks) topotecan (1.2 mgxm(-2)xd(-1)). Response to mainly determined magnetic resonance imaging. The expression Ras, phosphorylated mitogen activated protein kinase (p-MAPK), AKT (p-AKT), mammalian target rapamycin (p-mTOR) signal transducer activator transcription 3 (p-STAT3) were semiquantitatively assessed immunohistochemistry before initial treatment. RESULTS Five radiographic response. Three complete response, two partial Only progressive disease. 6-month progession-free survival (PFS) 33% median PFS 15 weeks, range 6 more than 60 Of three core analyzed this study, Ras/MAPK phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR likely be associated bevacizumab. In younger (ages < 50) simultaneous overexpression p-MAPK, p-AKT p-mTOR might crucial feature. CONCLUSIONS chemotherapeutic agents may an effective strategy glioma. Activated MAPK possible biomarkers selecting suitable targeted therapy.