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

doi:10.1093/neuonc/nov031

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 journal › Review article › peer-review

122 Scopus citations

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 language	English (US)
Pages (from-to)	1051-1063
Number of pages	13
Journal	Neuro-oncology
Volume	17
Issue number	8
DOIs	https://doi.org/10.1093/neuonc/nov031
State	Published - Aug 2015

Keywords

Clinical trial
Genomics
Glioblastoma
Precision medicine
Targeted therapy

ASJC Scopus subject areas

Oncology
Clinical Neurology
Cancer Research

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10.1093/neuonc/nov031

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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

Prados, MD, Byron, SA, Tran, NL, Phillips, JJ, Molinaro, AM, Ligon, KL, Wen, PY, Kuhn, JG, Mellinghoff, IK, De Groot, JF, Colman, H, Cloughesy, TF, Chang, SM, Ryken, TC, Tembe, WD, Kiefer, JA, Berens, ME, Craig, DW, Carpten, JD & Trent, JM 2015, 'Toward precision medicine in glioblastoma: The promise and the challenges', Neuro-oncology, vol. 17, no. 8, pp. 1051-1063. https://doi.org/10.1093/neuonc/nov031

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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",

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

year = "2015",

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doi = "10.1093/neuonc/nov031",

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AU - Molinaro, Annette M.

AU - Ligon, Keith L.

AU - Wen, Patrick Y.

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AU - De Groot, John F.

AU - Colman, Howard

AU - Cloughesy, Timothy F.

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AU - Tembe, Waibhav D.

AU - Kiefer, Jeffrey A.

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AU - Carpten, John D.

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AB - 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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Toward precision medicine in glioblastoma: The promise and the challenges

Abstract

Keywords

ASJC Scopus subject areas

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