Glioma targeted therapy: insight into future of molecular approaches

Abstract

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.

MD2 Is a Potential Biomarker Associated with Immune Cell Infiltration in Gliomas

“…We found that 8 immunoinhibitors (CD96, CSF1R, HAVCR2, IL10, IL10RB, LGALS9, PDCD1LG2, and TGFBR1, R > 0.5) and 6 immunostimulators (CD28, CD40, CD48, CD86, IL2RA, TMEM173, R > 0.5) were significantly associated with MD2 in gliomas ( Figure 6C ). Then, we detected the association between MD2 expression and nine immune checkpoints (PD1, PDL1, PDL2, LAG3, CTLA4, TIGIT, IDO1, CD276, CD47), which are promising immunotherapeutic targets for gliomas ( 48 , 49 ). The analysis revealed that MD2 is positively associated with PDL1, PDL2 and CD276 ( Figure 6D ).…”

Large-Scale Single-Cell and Bulk Sequencing Analyses Reveal the Prognostic Value and Immune Aspects of CD147 in Pan-Cancer

“…The immune system was first determined as a useful tool for targeting neoplastic disease by Wilhelm Bush and Friedrich Fehleisen in the nineteenth century ( 29 ). Since then, increasing studies have devoted to exploring the mechanism of tumor immunity for developing tumor immunotherapy ( 9 , 30 ). Tumor immunotherapy, differing from previous standards of therapies (including surgery, chemotherapy, and radiotherapy), has brought patients significant improvements in terms of quality of life and survival outcome ( 31 ).…”

Research progress of anti-glioma chemotherapeutic drugs (Review)

“…The median survival time of patients with glioma is only 15 months ( 11 ), whereas the 5-year survival rate is <10% ( 12 ). The etiology and mechanism underlying the pathogenesis of glioma remain unclear, but it has been demonstrated to show complex molecular characteristics, such as increases in chromosomes 7 and 19, loss of chromosomes 10 and 13, amplifications of EGFR and mouse double minute 2 homolog, mutations in PTEN, neurofibromatosis type 1, platelet-derived growth factor receptor α1, isocitrate dehydrogenase 1 and deletion of cyclin dependent kinase inhibitor 2A ( 13 , 14 ). Ionizing radiation exposure is also considered to be one of the causes of glioma ( 14 , 15 ).…”