**2. Defined molecular markers which changed our clinical attitude**

critically evaluated with regard to their histopathology, anatomical location, and

Primary brain tumors are a distinct group of pathologies due to their location, low incidence compared to other human tumors, histopathologic diversities, and unexpected response to treatment methods mainly caused by their peculiar genetic and molecular characteristics. Evaluating new important biomarkers which affect the etiopathogenesis of brain tumors may also help clinicians in consulting patients about prognosis, potential clinical studies, and following response to the treatment strategies [1]. Nowadays, the value of early detection of various types of cancer before metastasis has become a very significant issue. This approach may increase life expectancy and the quality of life in these patients [2]. It is known that one of the best management strategies of cancer is to predict its prognosis and response to the updated therapeutic procedures. In orderto achieve this, it is significant to considerthe blood, serum, plasma, or tissue biomarkers. Although the value of liquid biopsy in different human tumors is established, there is a lack of data regarding primary brain tumors [3]. Confluence of information suggested that genetic, epigenetic, functional or compositional heterogeneity of diseased and healthy tissues presented a major challenge to strategies to improve clinical outcome. [4]. Many molecules found in various fluids, tissues, and cell lines are produced either by the tumor itself, other tissues, or tumor microenvironment, in response to the presence of cancer or other associated conditions including inflammation. The scientists study on cancer search for proper candidate tumor markers and for identifying patients who face different diagnosis or clinical stages of cancer. This type of biomarkers must have some characteristics which can be used to estimate tumor volume, determine response to treat‐ ment, and assess disease recurrence through monitoring. Recent advancements have shown that amplifications/translocations, genetic mutations and changes in microarray-generated profiles (genetic signatures) are contributory in cancer development, metastasis and develop‐ ment of resistance against different therapeutics. These genetic signatures are referred according to the type of tumor marker or profile and may be associated with clinical out‐ comes or good prognosis or enhanced quality of life [3,4]. An ideal tumor marker is descri‐ bed as easily measurable, reliable, and cost-effective by use of an assay with high analytical sensitivity and specificity. Although we have developed a deeper understanding of the underlying mechanisms, there are only a few markers which have been used in routine applications and only a limited number of them can be used to identify patients or monitor

Gene overexpression is described as increase in copy number of genes or chromosomes (i.e., gene amplification) through increased transcriptional activity. It is known that imbalance between the gene repressors and gene activators or some epigenetic changes as DNA methylation or chromosomal translocations can alter transcriptional activity of the gene [3,4].

**Keywords:** gliomas, proliferation, apoptosis, cell cycle, gene

molecular-genetic fingerprints.

progression of cancer types and clinical staging.

**1. Introduction**

146 Neurooncology - Newer Developments

The use of biomarkers in glioblastoma (GBM) has been evaluated in a recent survey by neurooncologists [5]. Current evidences indicate that MGMT, EGFR, 1p/19q, EGFR, p53, phospha‐ tase andtensin homolog (PTEN) mutation ordeletion, EGFRvIII, IDH1/2, PDGFR, andPIK3CA are the most commonly used markers. But, use of these biomarkers claimed to be prognostic in GBM cases is still debated. There exist significantly varying clinical representations and cases of GBM, and the structure of the signaling molecules is highly complex, and therefore, use of these markers is not very common as of now. In addition, glioblastoma, still a hetero‐ geneous disease, also possesses additional difficulties such as having limited biomarkers to diagnosis and monitoring and therapeutic options, having poorly understood pathogenesis, and requiring individualized treatments. On the other hand, the discovery of new biomark‐ ers together with currently used markers can enable us to better stratify patients regarding treatment paradigms and clinical trials (**Figure 1**) [6,7].

**Figure 1.** Some signaling pathways with therapeutic implications in gliomas [7]. Some abbreviations are shown below. EGF: epidermal growth factor; PIP2, phosphatidylinositol phosphate-2; PIP3, phosphatidylinositol phosphate-2; PKC, protein kinase C; Grb2, growth factor receptor-bound protein-2; VEGF, vascular endothelial growth factor; S6K, p70 S6 kinase; mTOR, mammalian target of rapamycin; TF, transcription factors; SOS, son of sevenless molecule.
