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Individualized targeted therapy for glioblastoma: fact or fiction?


Weller, M; Stupp, R; Hegi, M; Wick, W (2012). Individualized targeted therapy for glioblastoma: fact or fiction? Cancer Journal, 18(1):40-44.

Abstract

PURPOSE: This review will address the current state of individualized cancer therapy for glioblastoma. Glioblastomas are highly malignant primary brain tumors presumably originating from neuroglial progenitor cells. Median survival is less than 1 year.
DESIGN: Recent developments in the morphologic, clinical, and molecular classification of glioblastoma were reviewed, and their impact on clinical decision making was analyzed.
RESULTS: Glioblastomas can be classified by morphology, clinical characteristics, complex molecular signatures, single biomarkers, or imaging parameters. Some of these characteristics, including age and Karnofsky Performance Scale score, provide important prognostic information. In contrast, few markers help to choose between various treatment options. Promoter methylation of the O-methylguanine methyltransferase gene seems to predict benefit from alkylating agent chemotherapy. Hence, it is used as an entry criterion for alkylator-free experimental combination therapy with radiotherapy. Screening for a specific type of epidermal growth factor receptor mutation is currently being explored as a biomarker for selecting patients for vaccination. Positron emission tomography for the detection of ανβ3/5 integrins could be used to select patients for treatment with anti-integrin antiangiogenic approaches.
DISCUSSION: Despite extensive efforts at defining biological markers as a basis for selecting therapies, most treatment decisions for glioblastoma patients are still based on age and performance status. However, several ongoing clinical trials may enrich the repertoire of criteria for clinical decision making in the very near future. The concept of individualized or personalized targeted cancer therapy has gained significant attention throughout oncology. Yet, data in support of such an approach to glioblastoma, the most malignant subtype of glioma, are limited, and personalized medicine plays a minor role in current clinical neuro-oncology practice. In essence, this concept proposes that tumors that are currently lumped together based on common morphologic features can be subclassified in a way that the resulting subentities are more homogeneous, for example, in molecular signatures and will therefore be amenable to selective therapeutic interventions. At present, the major "biomarkers" used to allocate treatment in glioblastoma are age and Karnofsky Performance Scale score, and these markers have so far survived all efforts at more sophisticated approaches to the management of this disease. Treatment allocation basically means intensity of treatment, especially the use of the standard-of-care or radiotherapy alone beyond age 65 to 70 years or below a Karnofsky Performance Scale score of 60.

PURPOSE: This review will address the current state of individualized cancer therapy for glioblastoma. Glioblastomas are highly malignant primary brain tumors presumably originating from neuroglial progenitor cells. Median survival is less than 1 year.
DESIGN: Recent developments in the morphologic, clinical, and molecular classification of glioblastoma were reviewed, and their impact on clinical decision making was analyzed.
RESULTS: Glioblastomas can be classified by morphology, clinical characteristics, complex molecular signatures, single biomarkers, or imaging parameters. Some of these characteristics, including age and Karnofsky Performance Scale score, provide important prognostic information. In contrast, few markers help to choose between various treatment options. Promoter methylation of the O-methylguanine methyltransferase gene seems to predict benefit from alkylating agent chemotherapy. Hence, it is used as an entry criterion for alkylator-free experimental combination therapy with radiotherapy. Screening for a specific type of epidermal growth factor receptor mutation is currently being explored as a biomarker for selecting patients for vaccination. Positron emission tomography for the detection of ανβ3/5 integrins could be used to select patients for treatment with anti-integrin antiangiogenic approaches.
DISCUSSION: Despite extensive efforts at defining biological markers as a basis for selecting therapies, most treatment decisions for glioblastoma patients are still based on age and performance status. However, several ongoing clinical trials may enrich the repertoire of criteria for clinical decision making in the very near future. The concept of individualized or personalized targeted cancer therapy has gained significant attention throughout oncology. Yet, data in support of such an approach to glioblastoma, the most malignant subtype of glioma, are limited, and personalized medicine plays a minor role in current clinical neuro-oncology practice. In essence, this concept proposes that tumors that are currently lumped together based on common morphologic features can be subclassified in a way that the resulting subentities are more homogeneous, for example, in molecular signatures and will therefore be amenable to selective therapeutic interventions. At present, the major "biomarkers" used to allocate treatment in glioblastoma are age and Karnofsky Performance Scale score, and these markers have so far survived all efforts at more sophisticated approaches to the management of this disease. Treatment allocation basically means intensity of treatment, especially the use of the standard-of-care or radiotherapy alone beyond age 65 to 70 years or below a Karnofsky Performance Scale score of 60.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:19 Sep 2012 07:35
Last Modified:05 Apr 2016 15:57
Publisher:Lippincott, Williams & Wilkins
ISSN:1528-9117
Additional Information:This is a non-final version of an article published in final form in Weller, M; Stupp, R; Hegi, M; Wick, W (2012). Individualized targeted therapy for glioblastoma: fact or fiction? Cancer Journal, 18(1):40-44.
Publisher DOI:10.1097/PPO.0b013e318243f6c9
PubMed ID:22290256
Permanent URL: http://doi.org/10.5167/uzh-64679

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