Combinatorial approaches to effective therapy in glioblastoma (GBM): Current status and what the future holds

Aug 8, 2022International reviews of immunology

Current and Future Combined Treatments for Glioblastoma Brain Cancer

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Abstract

No significant overall survival benefit has been achieved with standard treatments for glioblastoma.

Glioblastoma's aggressive nature is linked to biological diversity and dysfunctional metabolic processes.
The tumor's rigid blood-brain barrier and immunosuppressive environment contribute to its resistance to standard therapies.
Current treatments, including surgery, radiotherapy, and chemotherapy, have shown limited effectiveness.
There is a recognized need for advanced combinatorial treatment strategies to improve patient outcomes.
Recent developments in molecular biology and innovative therapies may offer new avenues for treatment.

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The aggressive and recurrent nature of glioblastoma is multifactorial and has been attributed to its biological heterogeneity, dysfunctional metabolic signaling pathways, rigid blood-brain barrier, inherent resistance to standard therapy due to the stemness property of the gliomas cells, immunosuppressive tumor microenvironment, hypoxia and neoangiogenesis which are very well orchestrated and create the tumor's own highly pro-tumorigenic milieu. Once the relay of events starts amongst these components, eventually it becomes difficult to control the cascade using only the balanced contemporary care of treatment consisting of maximal resection, radiotherapy and chemotherapy with temozolamide. Over the past few decades, implementation of contemporary treatment modalities has shown benefit to some extent, but no significant overall survival benefit is achieved. Therefore, there is an unmet need for advanced multifaceted combinatorial strategies. Recent advances in molecular biology, development of innovative therapeutics and novel delivery platforms over the years has resulted in a paradigm shift in gliomas therapeutics. Decades of research has led to emergence of several treatment molecules, including immunotherapies such as immune checkpoint blockade, oncolytic virotherapy, adoptive cell therapy, nanoparticles, CED and BNCT, each with the unique proficiency to overcome the mentioned challenges, present research. Recent years are seeing innovative combinatorial strategies to overcome the multifactorial resistance put forth by the GBM cell and its TME. This review discusses the contemporary and the investigational combinatorial strategies being employed to treat GBM and summarizes the evidence accumulated till date.

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Combinatorial approaches to effective therapy in glioblastoma (GBM): Current status and what the future holds

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