Advances in Glioblastoma Therapy: An Update on Current Approaches

Abstract

Glioblastoma multiforme (GBM) is a primary malignant brain tumor characterized by a high grade of malignancy and an extremely unfavorable prognosis. The current efficacy of established treatments for GBM is insufficient, necessitating the prompt development of novel therapeutic approaches. The progress made in the fundamental scientific understanding of GBM is swiftly translated into more advanced stages of therapeutic studies. Despite extensive efforts to identify new therapeutic approaches, GBM exhibits a high mortality rate. The current efficacy of treatments for GBM patients is insufficient due to factors such as tumor heterogeneity, the blood–brain barrier, glioma stem cells, drug efflux pumps, and DNA damage repair mechanisms. Considering this, pharmacological cocktail therapy has demonstrated a growing efficacy in addressing these challenges. Towards this, various forms of immunotherapy, including the immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have emerged as potential strategies for enhancing the prognosis of GBM. Current investigations are focused on exploring combination therapies to mitigate undesirable side effects and enhance immune responses against tumors. Furthermore, clinical trials are underway to evaluate the efficacy of several strategies to circumvent the blood–brain barrier (BBB) to achieve targeted delivery in patients suffering from recurrent GBM. In this review, we have described the biological and molecular targets for GBM therapy, pharmacologic therapy status, prominent resistance mechanisms, and new treatment approaches. We also discuss these promising therapeutic approaches to assess prospective innovative therapeutic agents and evaluated the present state of preclinical and clinical studies in GBM treatment. Overall, this review attempts to provide comprehensive information on the current status of GBM therapy.

Immunogenic cell death mediated TLR3/4-activated MSCs in U87 GBM cell line

“…Consequently, it cleaves and drives downstream signalling, leading to cell death. Following caspase-8 activation, subsequent signalling stimulates several downstream effector caspases [ 3 , 6 ,and7]] and the execution phase of apoptosis by causing nuclear and cell shrinkage. On the other hand, caspase-9 plays a critical role in the intrinsic pathway of apoptosis.…”

“…In this regard, different types of immunotherapy, including immune checkpoint blockade, oncolytic virotherapy, and vaccine therapy, have been offered to improve GBM management. Despite the progress in the field, GBM remains the most lethal tumour type, with limited therapy options and poor survival [ 6 ]. Considering the mentioned facts, new therapeutic approaches are needed to improve patient survival and effective clinical treatments to reinforce the tumour cell's sensitivity to chemotherapy.…”

Modelling Glioma Stem Cell-mediated Tumorigenesis Using Zebrafish PDX Systems

“…Glioblastoma (GBM) or grade IV, IDH-positive, astrocytoma is characterized by poor patient prognosis and limited sensitivity to standard of care treatment 1 . GBM accounts for 50% of all gliomas and 5-year survival rate of less than 10% 2,3 .…”

Synthesis and Characterization of ZIF-90 Nanoparticles as Potential Brain Cancer Therapy

“…Current glioblastoma therapy consists of a partial or complete surgical resection that can only be performed rarely, considering that tumor cells usually infiltrate the surrounding brain areas [ 4 ]. The treatment is integrated with radiotherapy targeted to the tumor bed, in combination with chemotherapy [ 5 , 6 ]. Adjuvant treatment after surgery can improve overall survival, for example, with monoclonal antibodies [ 7 ], but further investigations are still required to understand the mechanism and the efficacy of these approaches [ 5 ].…”

“…The main obstacle to the diagnosis and treatment of glioblastoma is the blood–brain barrier (BBB), which prevents more than 98% of contrast agents or therapeutic drugs from reaching the brain [ 8 , 9 , 10 , 11 ]. Therefore, a high dose of medication is usually required to treat glioblastoma, which often causes serious side effects [ 6 ]. Furthermore, therapeutic efficacy is limited by the high level of drug resistance of glioblastoma cells, which leads to an unfavorable prognosis and high relapse rates, with mutations of the tumor cells, both locally and distantly, from the site of primary origin of the cancer.…”