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Antiangiogenic therapy for glioblastoma: current status and future prospects


Batchelor, T T; Reardon, D A; de Groot, J F; Wick, W; Weller, M (2014). Antiangiogenic therapy for glioblastoma: current status and future prospects. Clinical Cancer Research, 20(22):5612-5619.

Abstract

Glioblastoma is characterized by high expression levels of proangiogenic cytokines and microvascular proliferation, highlighting the potential value of treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action. Ultimately, however, alternative proangiogenic signal transduction pathways are activated, leading to the development of resistance, even in tumors that initially respond. The identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority. Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma. However, future studies are warranted. Predictive markers may allow appropriate patient enrichment, combination with chemotherapy may ultimately prove successful in improving overall survival, and novel agents targeting multiple proangiogenic pathways may prove effective. See all articles in this CCR Focus section, "Discoveries, Challenges, and Progress in Primary Brain Tumors." Clin Cancer Res; 20(22); 5612-9. ©2014 AACR.

Abstract

Glioblastoma is characterized by high expression levels of proangiogenic cytokines and microvascular proliferation, highlighting the potential value of treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action. Ultimately, however, alternative proangiogenic signal transduction pathways are activated, leading to the development of resistance, even in tumors that initially respond. The identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority. Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma. However, future studies are warranted. Predictive markers may allow appropriate patient enrichment, combination with chemotherapy may ultimately prove successful in improving overall survival, and novel agents targeting multiple proangiogenic pathways may prove effective. See all articles in this CCR Focus section, "Discoveries, Challenges, and Progress in Primary Brain Tumors." Clin Cancer Res; 20(22); 5612-9. ©2014 AACR.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Date:15 November 2014
Deposited On:17 Nov 2014 17:37
Last Modified:08 Dec 2017 08:11
Publisher:American Association for Cancer Research
ISSN:1078-0432
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1158/1078-0432.CCR-14-0834
PubMed ID:25398844

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