Pharmacological strategies for improving the prognosis of glioblastoma

ABSTRACT

Introduction: Treatments for brain cancer have radically evolved in the past decade due to a better understanding of the interplay between the immune system and tumors of the central nervous system (CNS). However, glioblastoma multiforme (GBM) remains the most common and lethal CNS malignancy affecting adults.

Areas covered: The authors review the literature on glioblastoma pharmacologic therapies with a focus on trials of combination chemo-/immunotherapies and drug delivery platforms from 2015 to 2021.

Expert opinion: Few therapeutic advances in GBM treatment have been made since the Food and Drug Administration (FDA) approval of the BCNU-eluting wafer, Gliadel, in 1996 and oral temozolomide (TMZ) in 2005. Recent advances in our understanding of GBM have promoted a wide assortment of new therapeutic approaches including combination therapy, immunotherapy, vaccines, and Car T-cell therapy along with developments in drug delivery. Given promising preclinical data, these novel pharmacotherapies for the treatment of GBM are currently being evaluated in various stages of clinical trials.

KEYWORDS:

• Chimeric antigen receptor (CAR) t-cell therapy
• chemotherapy
• drug delivery
• glioblastoma
• immunotherapy
• liposomes
• polymersomes
• vaccine

Article highlights

• Glioblastoma multiforme (GBM) is a common, heterogeneous, and highly aggressive primary adult brain tumor with a median survival of less than two years.

• The current standard of care for newly diagnosed GBM includes surgical resection, chemotherapy with temozolomide (TMZ), and radiotherapy.

• While standalone therapies have not proven effective, current clinical trials of novel treatment combinations including TMZ, bevacizumab, nivolumab, ipilimumab, and/or radiotherapy are ongoing and are being tested in patients with MGMT methylated and MGMT unmethylated tumors to determine the effects of combined therapy on progression-free and overall survival.

• Immunogenic tumor-specific and tumor-associated antigens expressed by GBM cells can serve as targets for dendritic cell vaccines and CAR T-cell therapy, both of which have shown promising trial results when incorporated into standard treatment regimens.

• Drug delivery challenges including BBB penetration and toxicity to surrounding brain tissue can be circumvented through the strategic use of intracranial delivery platforms such as Gliadel®, nanoparticles, liposomes, and polymersomes.

• While GBM remains a devastating diagnosis, treatment regimens combining chemotherapeutics with immunotherapies and innovative drug delivery systems may provide the best chance for preventing tumor recurrence and increasing survival.

This box summarizes key points contained in the article.

Acknowledgments

All figures were created with BioRender.com.

Declaration of interest

B Tyler has received research funding from the National Institutes of Health and is co-owner for Accelerating Combination Therapies (including equity and options). B Tyler also declares that Ashvattha Therapeutics Inc. has also licensed one of her patents. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

EE Wicks is a research fellow supported by the Sarnoff Cardiovascular Research Foundation.