Toward precision medicine in glioblastoma: The promise and the challenges

Michael D. Prados, Sara A. Byron, Nhan L. Tran, Joanna J. Phillips, Annette M. Molinaro, Keith L. Ligon, Patrick Y. Wen, John G. Kuhn, Ingo K. Mellinghoff, John F. De Groot, Howard Colman, Timothy F. Cloughesy, Susan M. Chang, Timothy C. Ryken, Waibhav D. Tembe, Jeffrey A. Kiefer, Michael E. Berens, David W. Craig, John D. Carpten, Jeffrey M. Trent

Research output: Contribution to journalReview article

Abstract

Integrated sequencing strategies have provided a broader understanding of the genomic landscape and molecular classifications of multiple cancer types and have identified various therapeutic opportunities across cancer subsets. Despite pivotal advances in the characterization of genomic alterations in glioblastoma, targeted agents have shown minimal efficacy in clinical trials to date, and patient survival remains poor. In this review, we highlight potential reasons why targeting single alterations has yielded limited clinical efficacy in glioblastoma, focusing on issues of tumor heterogeneity and pharmacokinetic failure.We outline strategies to address these challenges in applying precision medicine to glioblastoma and the rationale for applying targeted combination therapy approaches that match genomic alterations with compounds accessible to the central nervous system.

Original languageEnglish (US)
Pages (from-to)1051-1063
Number of pages13
JournalNeuro-oncology
Volume17
Issue number8
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Clinical trial
  • Genomics
  • Glioblastoma
  • Precision medicine
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Prados, M. D., Byron, S. A., Tran, N. L., Phillips, J. J., Molinaro, A. M., Ligon, K. L., Wen, P. Y., Kuhn, J. G., Mellinghoff, I. K., De Groot, J. F., Colman, H., Cloughesy, T. F., Chang, S. M., Ryken, T. C., Tembe, W. D., Kiefer, J. A., Berens, M. E., Craig, D. W., Carpten, J. D., & Trent, J. M. (2015). Toward precision medicine in glioblastoma: The promise and the challenges. Neuro-oncology, 17(8), 1051-1063. https://doi.org/10.1093/neuonc/nov031