Genetics of glioblastoma multiforme: mitogenic signaling and cell cycle pathways converge

Abstract

Although the overall incidence of primary malignant brain tumours, 6.6 per 100,000 is relatively low compared to other tumours, with a median survival time of less than 2 years, they are nonetheless among the most lethal forms of cancer. Additionally, the fact that little is known about the etiology of malignant brain tumours as well as the paucity of identifiable risk factors in the disease makes their prevention and treatment especially challenging. Understanding the basic biology and tumorigenesis involved in the formation of malignant brain tumours is thus of paramount importance in developing new therapeutic options in their treatment. Glioblastoma Multiforme (GBM) is the leading cause of death among primary malignant brain tumours. Currently there are no treatment standards for the management of GBM, and therapies vary considerably across centers. The role of surgical resection and its effect on survival remain controversial – even after 75 years of experience in the treatment of malignant gliomas. Neurosurgeons vary in their opinions and practice patterns, and the management of GBM ranges from biopsy to total resection, followed by radiation in all cases and adjuvant chemotherapy in some cases. For many neurosurgeons surgical resection of high-grade gliomas remains the mainstay of treatment. On the other hand, given the highly aggressive nature, high rate of recurrence, and infiltrative nature of GBM, radical resection of GBM is advocated only by some surgeons. Nonetheless, the fact remains that despite numerous retrospective studies and a few prospective studies on the topic, surgical resection of GBMs has not been shown to significantly correlate with survival. Despite the varying treatment practices, it is well known that surgery and radiation treatment are superior to surgery alone, with the former survival time being 32 weeks vs. 14 weeks. This study was paramount in establishing treatment guidelines that recommended that all patients should be treated with XRT regardless of whether or not they had a gross total resection, partial resection, biopsy or no surgical resection at all of their tumour. However, no prospective data exists investigating whether surgical resection and radiation/chemotherapy versus biopsy and radiation/chemotherapy prolongs survival in GBM. Recently Sawaya et al. reported a 13-month median survival times for GBM patients undergoing surgery or biopsy. The randomized, doubleblind clinical trial comparing BCNU chemotherapy versus radiotherapy, as adjuvant treatment for GBM, was paramount is setting treatment guidelines for the role of post-operative XRT in the treatment of malignant gliomas. However, similar standards