The neural subtype was typified by the expression of neuron markers such as NEFL, GABRA1, SYT1, and SLC12A5, while often presenting themselves as normal cells upon pathological assessment.Many other genetic alterations have been described in glioblastoma, and the majority of them are clustered in two pathways, the RB and the PI3K/AKT. Glioblastomas have alterations in 68–78% and 88% of these pathways, respectively.Another important alteration is methylation of MGMT, a "suicide" DNA repair enzyme. Methylation impairs DNA transcription and expression of the MGMT gene. Since the MGMT enzyme can repair only one DNA alkylation due to its suicide repair mechanism, reserve capacity is low and methylation of the MGMT gene promoter greatly affects DNA-repair capacity. MGMT methylation is associated with an improved response to treatment with DNA-damaging chemotherapeutics, such as temozolomide. Cancer stem cells
Glioblastoma cells with properties similar to progenitor cells (glioblastoma cancer stem cells) have been found in glioblastomas. Their presence, coupled with the glioblastomas diffuse nature results in difficulty in removing them completely by surgery, and is therefore believed to be the possible cause behind resistance to conventional treatments, and the high recurrence rate. Glioblastoma cancer stem cells share some resemblance with neural progenitor cells, both expressing the surface receptor CD133. CD44 can also be used as a cancer stem cell marker in a subset of glioblastoma tumour cells. Glioblastoma cancer stem cells appear to exhibit enhanced resistance to radiotherapy and chemotherapy mediated, at least in part, by up-regulation of the DNA damage response.
Those receiving phenytoin concurrent with radiation may have serious skin reactions such as erythema multiforme and Stevens–Johnson syndrome. Corticosteroids, usually dexamethasone, can reduce peritumoral edema (through rearrangement of the blood–brain barrier), diminishing mass effect and lowering intracranial pressure, with a decrease in headache or drowsiness. Surgery
Surgery is the first stage of treatment of glioblastoma. An average GBM tumor contains 1011 cells, which is on average reduced to 109 cells after surgery (a reduction of 99%). Benefits of surgery include resection for a pathological diagnosis, alleviation of symptoms related to mass effect, and potentially removing disease before secondary resistance to radiotherapy and chemotherapy occurs.The greater the extent of tumor removal, the better. In retrospective analyses, removal of 98% or more of the tumor has been associated with a significantly longer healthier time than if less than 98% of the tumor is removed. The chances of near-complete initial removal of the tumor may be increased if the surgery is guided by a fluorescent dye known as 5-aminolevulinic acid. GBM cells are widely infiltrative through the brain at diagnosis, and despite a "total resection" of all obvious tumor, most people with GBM later develop recurrent tumors either near the original site or at more distant locations within the brain. Other modalities, typically radiation and chemotherapy, are used after surgery in an effort to suppress and slow recurrent disease. Radiotherapy
Subsequent to surgery, radiotherapy becomes the mainstay of treatment for people with glioblastoma. It is typically performed along with giving temozolomide.