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Neuro Oncol. 2015 Aug;17(8):1051-63. doi: 10.1093/neuonc/nov031. Epub 2015 May 1.

Toward precision medicine in glioblastoma: the promise and the challenges.

Author information

1
University of California San Francisco, San Francisco, California (M.D.P, J.J.P., A.M.M., S.M.C.); Translational Genomics Research Institute, Phoenix, Arizona (S.A.B., N.L.T., W.D.T., J.A.K., M.E.B., D.W.C., J.D.C., J.M.T.); Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.L.L., P.Y.W.); University of Texas Health Science Center, San Antonio, Texas (J.G.K.); Memorial Sloan-Kettering Cancer Center, New York, New York (I.K.M.); The University of Texas M.D. Anderson Cancer Center, Houston, Texas (J.F.d.G.); University of Utah Huntsman Cancer Institute, Salt Lake City, Utah (H.C.); University of California Los Angeles, Los Angeles, California (T.F.C.); Iowa Spine and Brain Institute, Waterloo, Iowa (T.C.R.).

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.

KEYWORDS:

clinical trial; genomics; glioblastoma; precision medicine; targeted therapy

PMID:
25934816
PMCID:
PMC4490873
DOI:
10.1093/neuonc/nov031
[Indexed for MEDLINE]
Free PMC Article

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