# Terahertz Time-Domain Spectroscopy of Glioma Patient Blood Plasma: Diagnosis and Treatment
## 1 Introduction  
The World Health Organization and the health departments of governments of all countries have listed tackling cancer as a top priority [1]. The main problem is late diagnosis, when the prognosis for a cure is unfavorable. Gliomas are one of the most grievousmalignant central nervous system tumors, and have a high mortality rate with a low survival rate, with severe disability and increased risk of recurrence [2; 3]. Glioblastoma multiforme (GBM) is one of the most aggressive, fast-moving, and deadliest types of gliomas [4; 5; 6]. According to the American Reggae Center for Tumors of the Nervous System statistics from the 2015-2019 period, the glioblastoma incidence was 14.2% among all tumors of the central nervous system and 50.1% among all malignant brain tumors [3]. Over the past few years, magnetic resonance imaging (MRI) has been the primary diagnostic tool for gliomas [7; 8; 9]. Fluid attenuated inversion recovery (FLAIR) imaging is a variant of MRI which provides high-quality tumor visualization. A combination of FLAIR MRI with the specific topological and textural features, and an automatic interpretable machine learning algorithm, provided a 97% accuracy of glioma detection and up to 95% accuracy on the glioma segmentation [10]. Computed tomography [11] and positron emission tomography [9; 12] are also used for glioma non-invasive diagnosis. These methods usually visualize gliomas of several centimeters of size [13] that do not correspond to the early tumor stage. The examination of the intraoperatively removed tumor or fine needle aspiration biopsy, using traditional histological, cytological, and histochemical methods, is used to establish or confirm a diagnosis [14]. However, histopathological features may be heterogeneous within a tumor, resulting in potential sampling errors and underestimating malignant biological behavior [6]. A GBM tumor contains small cells, characterized by polymorphism, anaplasia, and indistinct cellular borders, which have specific molecular patterns. Various molecular genetic features of gliomas have been discovered. Isocritate dehydrogenase1/2 (IDH1/2) mutations, 1p and 19q chromosomal deletions, and the methylation of O\({}^{6}\)-methylguanine-DNA methyltransferase were among the first discovered glioma biomarkers [15]. The accumulation of information about the genetic and molecular pathways of glioma development has led to a revision of the classification of CNS tumors based on molecular alterations [2; 6]. The glioma development molecular pathways include [16; 17; 18]:  
1. The dysregulation of the signaling pathway implemented through growth factors based on the amplification and mutation of tyrosine kinase receptors (TKRs). TKRs present a heterogeneous group of membrane proteins interacting with epithelial growth factor, vascular endothelial growth factor, and platelet growth factor. TRKs also interact with cytokines, hormones, and other signaling systems;
2. The activation of phosphotidylinositol-3-OH kinase (PI3K)/AKT/mTOR the intracellular signaling pathway ensures cell survival under certain conditions;
3. The inactivation of P53 protein and retinoblastoma suppression pathways;
4. Ras/Raf/MEK/ERK signaling pathway;
5. The regulation of cellular responses by protein kinase C (PKC), including protein secretion, gene expression, and cell proliferation;
6. Cell progression through pRB pathway suppression;
7. O\({}^{6}\)-methylguanine-DNA methyltransferase (MGMT);
8. TGF-\(\beta\) signaling [19]. The detection of molecular markers in tissues using genomic, proteomic, and metabolomic methods allows for a more accurate diagnosis of glioma in a small volume biopsy sample [2; 6; 20]. However, these methods are labor intensive and expensive. The tissue biopsy procedure is traumatic and cannot be used to control tumor treatment. As an alternative to tissue biopsy, the concept of a biofluid biopsy was introduced [21; 22].