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Review
. 2019 Jul;19(7):663-677.
doi: 10.1080/14737175.2019.1621169. Epub 2019 May 27.

Changing paradigms for targeted therapies against diffuse infiltrative gliomas: tackling a moving target

Candice D Carpenter  1 , Iyad Alnahhas  2 , Javier Gonzalez  1   2 , Pierre Giglio  1   2 , Vinay K Puduvalli  1   2
Affiliations
Review

Changing paradigms for targeted therapies against diffuse infiltrative gliomas: tackling a moving target

Candice D Carpenter et al. Expert Rev Neurother. 2019 Jul.

Abstract

Introduction: Gliomas are highly heterogeneous primary brain tumors which result in a disproportionately high degree of morbidity and mortality despite their locoregional occurrence. Advances in the understanding of the biological makeup of these malignancies have yielded a number of potential tumor-driving pathways which have been identified as rational targets for therapy. However, early trials of agents that target these pathways have uniformly failed to yield improvement in outcomes in patients with malignant gliomas. Areas covered: This review provides an overview of the most common biological features of gliomas and the strategies to target the same; in addition, the current status of immunotherapy and biological therapies are outlined and the future directions to tackle the challenges of therapy for gliomas are examined. Expert opinion: The limitations of current treatments are attributed to the inability of most of these agents to cross the blood-brain barrier and to the intrinsic heterogeneity of the tumors that result in treatment resistance. The recent emergence of immune-mediated and biological therapies and of agents that target metabolic pathways in gliomas have provided strategies that may overcome tumor heterogeneity and ongoing trials of such agents are anticipated to yield improved outcomes.

Keywords: Gliomas; immunotherapy; targeted therapies; treatment resistance; tumor heterogeneity.

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Conflict of interest statement

Declaration of interest

VK Puduvalli has acted as Site Principal investigator for trails by DNAtrix, Novartis, Bexion, Celldex. Consultant Orbus Therapeutics, SK Life Science and Threshold Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

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