Molecularly Targeted Clinical Trials

Matthew A Smith-Cohn; Orieta Celiku; Mark R Gilbert

doi:10.1016/j.nec.2020.12.002

Molecularly Targeted Clinical Trials

Neurosurg Clin N Am. 2021 Apr;32(2):191-210. doi: 10.1016/j.nec.2020.12.002. Epub 2021 Feb 18.

Authors

Matthew A Smith-Cohn¹, Orieta Celiku², Mark R Gilbert³

Affiliations

¹ Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Building 37, Room 1016, Bethesda, MD 20892, USA; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
² Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Building 37, Room 1142, Bethesda, MD 20892, USA.
³ Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].

PMID: 33781502
DOI: 10.1016/j.nec.2020.12.002

Abstract

Glioblastoma remains incurable despite advances in surgery, radiation, and chemotherapy, underscoring the need for new therapies. The genetic heterogenicity, presence of redundant molecular pathways, and the blood-brain barrier have limited the applicability of molecularly targeted agents. The therapeutic benefit seen with a small subset of patients suggests, however, that patient selection is critical. Recent investigations show that molecularly targeted synthetic lethality is a promising complementary approach. The article provides an overview of the challenges of molecularly targeted therapy in adults with glioblastoma, including current trials and future therapeutic directions.

Keywords: Blood-brain barrier; Glioblastoma; Heterogenicity; Synthetic lethality; Targeted therapy.

Published by Elsevier Inc.

Publication types

Review

MeSH terms

Adult
Blood-Brain Barrier
Brain Neoplasms* / drug therapy
Brain Neoplasms* / genetics
Clinical Trials as Topic
Glioblastoma* / drug therapy
Glioblastoma* / genetics
Humans
Molecular Targeted Therapy