Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma

Abstract

Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensitymodulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development for patients, their families, and medical professionals alike.

Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme

“…In the clinic, the majority of patients with primary GBM experience disease recurrence within a few months because of the high infiltrative capacity of residual GBM cells. 2 Although the mechanism is still elusive, radioresistance and enhanced invasive potential of glioma cells after radiotherapy have been reported. 4,30,31 In addition, MerTK and Axl have recently been implicated in chemoresistance of astrocytoma cells.…”

“…1 Although the median survival after diagnosis of GBM patients has improved from 10 to 14 months in the last decade, there is still no effective treatment for this malignant cancer. 2 Thus, the demand remains for therapies improving survival and maintaining quality of life.…”

Standard of care therapy for malignant glioma and its effect on tumor and stromal cells

“…There have been a number of primary papers and reviews published over the past several years that discuss the role of signal transduction pathways in gliomagenesis and the potential therapeutic utility of signal transduction inhibitors (Huse and Holland, 2010). Indeed, a plethora of signal transduction inhibitors have been developed and several are currently being tested in clinical trials for glioma (Arko et al, 2010;Van Meir et al, 2010). Unfortunately, preliminary findings from many of these trials suggest that these agents have not significantly influenced the course of the disease when compared with standard of care therapy (Arko et al, 2010).…”

FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells

“…Currently, despite the standard treatment regimen including the maximum extent of surgical resection plus postoperative chemoradiotherapy, the improvement of the median survival period of GBM is still unsatisfactory, which is largely attributed to the therapeutic resistance to temozolomide (TMZ) 1. Previous research has already implicated a complicated molecular network of signaling pathways in mediating the malignance of glioma.…”