Toward precision medicine in glioblastoma: the promise and the challenges

被引：171

作者：

Prados, Michael D. ^{[1
]}

Byron, Sara A. ^{[2
]}

Tran, Nhan L. ^{[2
]}

Phillips, Joanna J. ^{[1
]}

Molinaro, Annette M. ^{[1
]}

Ligon, Keith L. ^{[3
]}

Wen, Patrick Y. ^{[3
]}

Kuhn, John G. ^{[4
]}

Mellinghoff, Ingo K. ^{[5
]}

de Groot, John F. ^{[6
]}

Colman, Howard ^{[7
]}

Cloughesy, Timothy F. ^{[8
]}

Chang, Susan M. ^{[1
]}

Ryken, Timothy C. ^{[9
]}

Tembe, Waibhav D. ^{[2
]}

Kiefer, Jeffrey A. ^{[2
]}

Berens, Michael E. ^{[2
]}

Craig, David W. ^{[2
]}

Carpten, John D. ^{[2
]}

Trent, Jeffrey M. ^{[2
]}

机构：

[1] Univ Calif San Francisco, San Francisco, CA 94143 USA

[2] Translat Genom Res Inst, Phoenix, AZ USA

[3] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA

[4] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA

[5] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[6] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[7] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA

[8] Univ Calif Los Angeles, Los Angeles, CA USA

[9] Iowa Spine & Brain Inst, Waterloo, IA USA

来源：

NEURO-ONCOLOGY | 2015年 / 17卷 / 08期

关键词：

clinical trial; genomics; glioblastoma; precision medicine; targeted therapy; NEWLY-DIAGNOSED GLIOBLASTOMA; BRAIN-TUMOR CONSORTIUM; CONVECTION-ENHANCED DELIVERY; INTEGRATED GENOMIC ANALYSIS; RECURRENT MALIGNANT GLIOMA; FACTOR RECEPTOR INHIBITORS; TYROSINE KINASE INHIBITOR; PROGRESSION-FREE SURVIVAL; RANDOMIZED PHASE-III; ADJUVANT TEMOZOLOMIDE;

D O I：

10.1093/neuonc/nov031

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：1051 / 1063

页数：13

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