Preliminary application of new chemotherapeutic strategy targeting glioma stem cells

Abstract

Objective To explore the safety and efficacy of new targeting chemotherapy strategy of glioma stem cells (GSCs) and its preliminary applications. Methods A total of 12 patients with glioblastoma (GBM) admitted to Department of Neurosurgery, the Second Affiliated Hospital of Soochow University from January 2013 to April 2017 were enrolled into this retrospective study. The patients underwent new chemotherapy if tumor analysis showed ABCG2 (+ ), MGMT methylation (-), or recurrence of GBM after standardized treatment. The temozolomide (TMZ), sodium valproate (VPA) and nicardipine combined drug regimen was implemented for 6 cycles. Evaluation of the efficacy with KPS (Karnofsky performance status scale), Response Evaluation Criteria in Solid Tumors of WHO and lifetime was carried out. Results Immunohistochemical examination of tumor tissues in the 12 patients showed that ABCG2 and MGMT were expressed at different levels. Methylation-specific PCR (polymerase chain reaction) results showed that the MGMT methylation was negative in the enrolled patients. Enhanced MR scan was used to evaluate treatment efficacy. Complete remission was achieved in 2 cases, partial remission in 3 cases, stable disease in 2 cases, and progressive disease in 5 cases (including 4 deaths). The average survival time was 18.4±10.9 months. There were no treatment-related serious adverse events. The average KPS post treatment was 51.7±31.6. Conclusion The new chemotherapy strategy of TMZ combined with VPA and nicardipine targeting GSCs has certain curative effect on chemo-resistant GBM and those drug regimens could be relatively well tolerated. Key words: Glioblastoma; Neoplastic stem cells; ATP-binding cassette transporter G2; Chemotherapy