4.7 Review

Glioblastoma targeted therapy: updated approaches from recent biological insights

Journal

ANNALS OF ONCOLOGY
Volume 28, Issue 7, Pages 1457-1472

Publisher

ELSEVIER
DOI: 10.1093/annonc/mdx106

Keywords

glioma; cancer genomics; targeted therapies; precision medicine; personalized medicine; biomarkers

Categories

Funding

  1. Fondation pour la Recherche Medicale [FDM 41635]
  2. NIH [R01CA188288, R01 CA170592, P50 CA165962]
  3. Ivy Foundation
  4. PLGA Foundation
  5. ABC2 Foundation

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Glioblastoma (WHO grade IV astrocytoma) is the most frequent primary brain tumor in adults, representing a highly heterogeneous group of neoplasms that are among the most aggressive and challenging cancers to treat. An improved understanding of the molecular pathways that drive malignancy in glioblastoma has led to the development of various biomarkers and the evaluation of several agents specifically targeting tumor cells and the tumor microenvironment. A number of rational approaches are being investigated, including therapies targeting tumor growth factor receptors and downstream pathways, cell cycle and epigenetic regulation, angiogenesis and antitumor immune response. Moreover, recent identification and validation of prognostic and predictive biomarkers have allowed implementation of modern trial designs based on matching molecular features of tumors to targeted therapeutics. However, while occasional targeted therapy responses have been documented in patients, to date no targeted therapy has been formally validated as effective in clinical trials. The lack of knowledge about relevant molecular drivers in vivo combined with a lack of highly bioactive and brain penetrant-targeted therapies remain significant challenges. In this article, we review the most promising biological in-sights that have opened the way for the development of targeted therapies in glioblastoma, and examine recent data from clinical trials evaluating targeted therapies and immunotherapies. We discuss challenges and opportunities for the development of these agents in glioblastoma.

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