Journal
GYNECOLOGIC ONCOLOGY
Volume 141, Issue 1, Pages 80-85Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2015.12.033
Keywords
Anti-angiogenesis therapy; Prediction of response; Resistance; Escape mechanisms
Categories
Funding
- National Institutes of Health [CA177909, CA016672, CA109298, UH3TR000943, P50 CA083639, P50 CA098258]
- Cancer Prevention and Research Institute of Texas [RP110595, RP120214]
- Ovarian Cancer Research Fund, Inc.
- RGK Foundation
- Gilder Foundation
- Judi A Rees ovarian cancer research fund
- Blanton-Davis Ovarian Cancer Research Program
- Betty Anne Asche Murray Distinguished Professorship
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Many clinical trials have demonstrated the benefit of anti-angiogenesis therapy in the treatment of gynecologic cancer. However, these benefits have often been in terms of progression-free rather than overall survival and in some cases, the magnitude of benefit demonstrated in the pivotal phase 3 trials has been disappointing when compared with the percentage of patients who responded in earlier phase 2 trials. Two potential explanations for this are the current inability to stratify patients according to chance of benefit and the development of resistance mechanisms within the tumor. In this article, we review the prediction of response and the proposed resistance and escape mechanisms involved in anti-angiogenesis therapy, including the up-regulation of alternative proangiogenic pathways, vascular co-option, and resistance to hypoxia. These insights may offer a personalized strategy for anti-angiogenesis therapy and help us to consider the best selection of other therapies that should be combined with anti-angiogenesis therapy to improve the outcome of patients with gynecologic cancer. (C) 2016 Elsevier Inc. All rights reserved.
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