Introduction: Glioblastoma: an update on pathophysiology and management strategies.

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Glioblastoma multiforme remains an enigma for neu­ rooncology; our understanding has progressed, but the prognosis is still poor. In this issue of Neurosurgical Focus, the emphasis is on presenting current understanding of the pathophysiology of the disease and the manage­ ment strategies that stem from it. The issue can be divided into current management strategies and future treatments based on recent advances in understanding glioblastoma pathophysiology, including cancer stem cells, angiogen­ esis, and tumor heterogeneity. The first part of the issue is devoted to an evaluation of treatment methods available to patients today. From an operative standpoint, Hawasli et al. present a timely ar­ ticle on the use of stereotactic laser ablation of high­grade gliomas, a procedure that is available to most neurosur­ geons using the current armamentarium of imaging and ablative equipment. Lescher and colleagues assert that the time frame for the evaluation of postoperative chang­ es versus residual tumor is important in determining the extent of resection, given increasing data showing sur­ vival benefits with radiographically grossor near-total resections. From a medical perspective, Barbagallo et al. report data on long­term treatment with temozolomide, whereas Pompili et al. describe palliative care and end of life issues for patients with glioblastoma. The second part of this issue emphasizes the role of future treatments that will stem from recent advances in understanding the pathophysiology of glioblastoma mul­ tiforme. Sundar et al. present a timely review on the role of cancer stem cells in glioblastoma, which is followed by Khan and Ehtesham’s article on treatment based on targeting glioma stem cells. The importance and role of angiogenesis in glioblastoma pathophysiology is demon­ strated in Womeldorff et al.’s article on the role of hy­ poxia­inducible factor­1, hypoxia, and cytokine­induced angiogenesis. Understanding the role of angiogenesis leads to a better evaluation of the role of bevacizumab in glioblastoma treatment (Castro and Aghi) and the role of MET activation as a reaction to its use (Awad et al.). Tumor heterogeneity and the microenvironment are well recognized in glioblastoma, but recent advances in mo­ lecular genomics enable not only a precise diagnosis, but also prognostic implications. Aum et al. present a pre­ cise overview of the molecular and cellular heterogene­ ity found in glioblastoma. Golden et al. report preclinical data on the role of chloroquine and autophagy in glioblas­ toma. Two genes with important prognostic implications have recently been identified: IDH (Agnihotri et al.) and WT1 (Broaddus et al.). Identification of these targets can lead to new molecularly targeted therapies (Lau et al.). Treatment of glioblastoma requires a multidisciplin­ ary approach based on understanding the pathophysiol­ ogy of the disease, which will eventually lead to a better prognosis and quality of life for our patients. (http://thejns.org/doi/abs/10.3171/2014.9.FOCUS14677)