Introduction: Gliomas are the most common type of primary brain tumors, accounting for about 30-80 percent of all brain tumors and malignant tumors, respectively. World Health Organization (WHO) has classified tumors into four grades, based on malignancy, with grade I tumors having the least malignant behavior and grade IV tumors the most. Glioblastoma, previously known as glioblastoma multiform (GBM), belongs to grade four, which is the most malignant form. It can also be the most feared type of primary brain tumor not only for its aggressiveness and high levels of proliferation but also for its effects on the quality of life. This tumor, on average, usually develops at the age of 64 with a 14.8 percent of survival rate at 2 years. Therefore, among common gliomas, glioblastoma has the least survival rate. There is also a molecular classification for glioblastoma that comprises of four subtypes, based on different gene alterations. These subtypes include classic, mesenchymal, proneural, and neural glioblastomas. Despite different methods available for diagnosis, treatment, and management of patients with glioblastoma, prognostic factors such as age, gender, the extent of tumor resection, and neurological status play an important role in the overall outcome of a patient. While various factors can be used to classify glioblastoma, generally, it is characterized into primary and secondary glioblastomas, which was first presented by Hans Joachim Scherer (1906 - 1945), the German neuropathologist.
Methods: This review concentrates on cellular and genetic drawbacks that can lead to the appearance of glioblastoma. National Center for Biotechnology Information (NCBI) was the main source used for writing this review article, followed by Google scholar.
Results: Several genetic alterations and cellular pathways are involved in the appearance and progression of glioblastoma, including loss of heterozygosity (LoH), TP53 mutation, isocitrate dehydrogenase 1 (IDH1) mutation, P16INK4/RB1 pathway, and EGFR/PTEN/Akt/mTOR pathway. The majority (70%) of primary glioblastomas are caused by LoH, and it mostly occurs in older people. Secondary glioblastoma is mainly manifested by TP53 mutation and usually affects younger people. Understanding the alterations and cellular mechanisms involved in glioblastoma is important in developing new therapeutic regimes. Surgery, radiation therapy, temozolomide, and TTFields are the four most important therapeutic options available for treating patients.
Conclusion: Glioblastoma is a malignant and hardly-survived tumor that uses different cellular pathways and manifests various genetic alterations for its development. LOH10q and TP53 mutation were the most frequent gene alterations recognized in primary and secondary glioblastoma, respectively. Due to recent advances in understanding the cellular and molecular complexity of this tumor, several promising medical approaches have been included in treatment strategies, including the usage of nutlins, TMZ, and TTFields. Although this tumor is the toughest among gliomas, there is hope for new and better therapeutic options, which may ease the diagnosis and treatment process of this invasive tumor.