Glioblastoma Multiforme—A Look at the Past and a Glance at the Future

Abstract

Gliomas are the most common type of brain tumor that occur in adults and children. Glioblastoma multiforme (GBM) is the most common, aggressive form of brain cancer in adults and is universally fatal. The current standard-of-care options for GBM include surgical resection, radiotherapy, and concomitant and/or adjuvant chemotherapy. One of the major challenges that impedes success of chemotherapy is the presence of the blood–brain barrier (BBB). Because of the tightly regulated BBB, immune surveillance in the central nervous system (CNS) is poor, contributing to unregulated glioma cell growth. This review gives a comprehensive overview of the latest advances in treatment of GBM with emphasis on the significant advances in immunotherapy and novel therapeutic delivery strategies to enhance treatment for GBM.

Small, Smart, and LDLR-Specific Micelles Augment Sorafenib Therapy of Glioblastoma

“…In particular, SF therapy is considered as a new and potent strategy in that it could not only effectively inhibit cancer cell proliferation and prevent angiogenesis by blocking the RAF-MEK-ERK (MAPK) pathway, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR) but also selectively deplete human GBM tumor-initiating cells (GICs) . SF has been approved for clinical therapy of hepatocellular carcinoma, advanced renal cell carcinoma, and differentiated thyroid cancer and also shows clinical benefits for lung cancer, breast cancer, and melanoma. , Several clinical trials with SF, as monotherapy or combination therapy with current treatments, for example, bevacizumab, erlotinib, and tipifarnib, for treating GBM failed to meet the clinical endpoints, likely as a result of the blood–brain barrier (BBB) and inferior GBM delivery. , The clinical use of SF is also disturbed by its poor bioavailability and high and frequent dosing that causes toxicity issues. , Several nanosystems such as lipopolyplex and hydrogels have been studied to enhance SF delivery for hepatocellular carcinoma. , Notably, intratumoral administration of SF-loaded lipid nanocapsules was reported to efficiently treat GBM xenografts …”

“…13,14 Several clinical trials with SF, as monotherapy or combination therapy with current treatments, for example, bevacizumab, 15 erlotinib, 16 and tipifarnib, 9 for treating GBM failed to meet the clinical endpoints, likely as a result of the blood−brain barrier (BBB) and inferior GBM delivery. 17,18 The clinical use of SF is also disturbed by its poor bioavailability and high and frequent dosing that causes toxicity issues. 9,19 Several nanosystems such as lipopolyplex and hydrogels have been studied to enhance SF delivery for hepatocellular carcinoma.…”

Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

“…Currently, the treatment of GBM comprises firstly using surgical resection to reduce the tumor load and prolong the survival time. 119 Then combine DC vaccines with radiotherapy, chemotherapy, or both to induce DNA damage and endoplasmic reticulum stress to stimulate cell death, release chemokines and cytokines to increase the DC stimulation signals, thus supplementing the effect of anti‐tumor DC vaccines. We can also combine specific targeted therapy to block the pathways besides activating DC, such as targeting the BBB to increase drug delivery, targeting signaling pathways such as p53, RTK and Rb, 94 or cytokines to specifically block MDSCs, Tregs and microglia.…”

“…Targeting multiple pathways through DC vaccines combined with other therapies might be an important method to combat immunosuppression in the TME. Currently, the treatment of GBM comprises firstly using surgical resection to reduce the tumor load and prolong the survival time 119 . Then combine DC vaccines with radiotherapy, chemotherapy, or both to induce DNA damage and endoplasmic reticulum stress to stimulate cell death, release chemokines and cytokines to increase the DC stimulation signals, thus supplementing the effect of anti‐tumor DC vaccines.…”

A Computational Framework to Identify Biomarkers for Glioma Recurrence and Potential Drugs Targeting Them

“…Currently, the conventional therapeutic regimen for gliomas is surgical resection followed by radiotherapy and chemotherapy. However, the curative effect is far from satisfaction and recurrence is still the major obstacle to the success of chemoradiotherapy since the majority of GBM would experience recurrence within 6.2 months after diagnosis ( Bähr et al, 2009 ; King and Benhabbour, 2021 ). Therefore, it is imperative to find new therapeutic target and novel therapeutic strategies for patient with gliomas.…”