Novel therapeutics for brain tumors: current practice and future prospects

ABSTRACT

Introduction: Malignant gliomas are the most common and aggressive primary brain tumor with current available therapies increasing median survival to a modest 20 months. Multiple preclinical research efforts aim to further this improvement through advances in therapeutic options for these patients.

Areas covered: The unique obstacles that must be managed in developing and delivering safe and efficacious therapeutics into the central nervous system are reviewed. We describe the successes and challenges in local drug delivery in the field of neuro-oncology and explore convection enhanced delivery and high frequency ultrasound as tools for safe and effective delivery. Drug delivery systems are described in addition to combination therapies that are being tested both preclinically, as well as ones currently in clinical trials. The field of immunotherapy is also discussed along with specific considerations as it relates to the brain’s microenvironment.

Expert opinion: While there have been incremental advances in brain cancer therapeutics over the last few years, novel therapeutics are expanding with multiple opportunities in neuro-oncology. Overcoming the brain’s unique challenges might allow for breakthroughs and discoveries in the future.

KEYWORDS:

• Blood-brain-barrier
• glioma
• immunotherapy
• nanoparticle
• polymer
• ultrasound

Article highlights

• Successes and challenges are discussed regarding optimizing new therapeutics for the treatment of malignant gliomas.

• Drug delivery systems such as biodegradable polymers, nanoparticles, and liposomes delivering standard chemotherapeutic agents as well as novel targeted compounds and combinations of drugs with complimentary mechanisms of action are presented.

• Immunotherapy in the context of local chemotherapy for the treatment of brain tumors is discussed.

Declaration of interest

H Brem has research funding from National Institute of Health, Johns Hopkins University, Arbor Pharmaceuticals, Bristol-Myers Squibb, Acuity Bio Corp, and Philanthropy. H Brem is also a Consultant for AsclepiX Therapeutics, StemGen, InSightec, Accelerating Combination Therapies*, Camden Partners*, LikeMinds, Inc*, Galen Robotics, Inc.*, and Nurami Medical* (*includes equity or options). 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

This paper was funded by the Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.