期刊
NEURO-ONCOLOGY
卷 17, 期 8, 页码 1051-1063出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/nov031
关键词
clinical trial; genomics; glioblastoma; precision medicine; targeted therapy
资金
- Ben and Catherine Ivy Foundation
- NATIONAL CANCER INSTITUTE [P30CA008748, P50CA097257] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS080944, R01NS081117] Funding Source: NIH RePORTER
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.
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