Prospects of biological and synthetic pharmacotherapies for glioblastoma

ABSTRACT

Introduction: The field of neuro-oncology has experienced significant advances in recent years. More is known now about the molecular and genetic characteristics of glioma than ever before. This knowledge leads to the understanding of glioma biology and pathogenesis, guiding the development of targeted therapeutics and clinical trials. The goal of this review is to describe the state of basic, translational, and clinical research as it pertains to biological and synthetic pharmacotherapy for gliomas.

Areas covered: Challenges remain in designing accurate preclinical models and identifying patients that are likely to respond to a particular targeted therapy. Preclinical models for therapeutic assessment are critical to identify the most promising treatment approaches.

Expert opinion: Despite promising new therapeutics, there have been no significant breakthroughs in glioma treatment and patient outcomes. Thus, there is an urgent need to better understand the mechanisms of treatment resistance and to design effective clinical trials.

KEYWORDS:

• Glioma
• immune checkpoint inhibitors
• gene therapy
• IDH1 mutation
• immunotherapy

Article Highlights

• In this review we cover the breadth of new therapeutic strategies that have emerged as potential treatment options for glioma.

• We provide an insight into the basic mechanisms involved in the development of resistance against targeted therapies.

• We present the importance of multi-modal therapies to address the heterogeneity of known mutations present in the different glioma subtypes.

Declaration of interest

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 relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) Grants R21-NS091555 to MG Castro, A Schwendeman, and PR Lowenstein; National Institutes of Health/National Cancer Institute (NIH/NCI) Grants UO1-CA224160 to MG Castro, and PR Lowenstein; R37NS094804 and R01NS105556 to MG Castro; R01NS076991, R01NS082311, and R01NS096756 to PR Lowenstein; National Institutes of Health/National Cancer Institute (NIH/NIC) Grant T32-0CA009676 to MS Alghamri and SV Carney; National institutes of Health/National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB) Grant R01-EB022563 to JJ Moon, PR Lowenstein, and MG Castro; University of Michigan M-Cube; the Center for RNA Biomedicine; the Department of Neurosurgery; the University of Michigan Rogel Comprehensive Cancer Center; Leah’s Happy Hearts Foundation; the ChadTough Foundation, the Smiles for Sophie Forever Foundation, the Pediatric Brain Tumor Foundation, and the Biointerfaces Institute at the University of Michigan.