Anti-cancer Therapies in High Grade Gliomas

Abstract

High grade gliomas represent one of the most aggressive and treatment-resistant types of human cancer, with only 1–2 years median survival rate for patients with grade IV glioma. The treatment of glioblastoma is a considerable therapeutic challenge; combination therapy targeting multiple pathways is becoming a fast growing area of research. This review offers an up-to-date perspective of the literature about current molecular therapy targets in high grade glioma, that include angiogenic signals, tyrosine kinase receptors, nodal signaling proteins and cancer stem cells related approaches. Simultaneous identification of proteomic signatures could provide biomarker panels for diagnostic and personalized treatment of different subsets of glioblastoma. Personalized medicine is starting to gain importance in clinical care, already having recorded a series of successes in several types of cancer; nonetheless, in brain tumors it is still at an early stage.

Bergamottin, a natural furanocoumarin abundantly present in grapefruit juice, suppresses the invasiveness of human glioma cells via inactivation of Rac1 signaling

“…The highly invasive feature of malignant gliomas renders them refractory to surgery, radiation and chemotherapy (2). Despite improvement in treatment modalities, the median survival time for malignant gliomas is only between 1 and 2 years (3,4). Therefore, it is of importance to develop novel effective therapies against invasive gliomas.…”

Insights into molecular therapy of glioma: current challenges and next generation blueprint

“…There are two important considerations that effect glioma therapy; first, numerous RTKs are co-activated in glioma cells [103] ; and second, issues of acquired resistance. Thus, a combination of surgery, chemotherapy and RT are essential for sensitizing the glioma cells to [75,76] Platelet-derived growth factor (PDGF) [77][78] Epidermal Growth Factor Receptors (EGFRs) [76] PI3K and Akt pathway and PI3K/Akt [75,76,79,80] Mammalian target of rapamycin (mTOR) [81,82] Notch pathway [83][84][85] Matrix metalloproteinase (MMP) family [75] • Upregulation of VEGF and its receptors VEGFR-1 and VEGFR-2 activated by VEGF-A is often allied with cell proliferation, tumor invasion, migration and permeability • Proliferating and migrating endothelial cells are regulated by VEGFR incited Ras/Raf/mitogenactivated protein kinase and phospholipase C-γ/protein kinase C signaling cascades • VEGF ligand promotes tumor growth by both autocrine and paracrine manner…”

“…Expression of the stem cell-associated protein CD133 helps in the identification and isolation of GBM CSCs. It has been recently determined that CD133+ GBM cells are more radioresistant than CD133-cells [75] . In spite of having an intact G 2 checkpoint, CD133+ cells lack the intra-S-phase checkpoint.…”

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

“…Recently, the WHO classification has been modified to include molecular criteria, such as IDH mutations for diffuse astrocytoma and GBM, or the epigenetic mark H3K27M mutation for diffuse midline glioma, to provide more precise diagnosis and treatment 6. However, the quest for potential therapeutic targets remains unfulfilled;7, 8 thus, new strategies are emerging to explore the molecular basis of brain tumour development for clinical exploitation.…”