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Targeting the Angiopoietin-2/Tie-2 axis in conjunction with VEGF signal interference
Nikolett M Biel1, Dietmar W Siemann2
1Department of Pathology, University of Florida College of Medicine, 1395 Center Drive, Gainesville, FL 32610, USA.
Abstract:
Anti-angiogenic therapies target the tumor vasculature, impairing its development and growth. It was hypothesized over 40 years ago by the late Judah Folkman and Julie Denekamp that depriving a tumor of oxygen and nutrients, by targeting the tumor vasculature, could have therapeutic benefits. Identification of growth factors and signaling pathways important in angiogenesis subsequently led to the development of a series of anti-angiogenic agents that over the past decade have become part of the standard of care in several disease settings. Unfortunately not all patients respond to the currently available anti-angiogenic therapies while others become resistant to these agents following prolonged exposure. Identification of new pathways that may drive angiogenesis led to the development of second-generation anti-angiogenic agents such as those targeting the Ang-2/Tie2 axis. Recently, it has become clear that combination of first and second generation agents targeting the blood vessel network can lead to outcomes superior to those using either agent alone. The present review focuses on the current status of VEGF and Ang-2 targeted agents and the potential utility of using them in combination to impair tumor angiogenesis.
Insights
Anti-angiogenic therapies target tumor blood vessels to inhibit growth. Combining first-generation (VEGF) and second-generation (Ang-2) agents shows promise for improved outcomes in cancer treatment.
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Anti-angiogenic therapies aim to starve tumors by targeting their blood supply.
- Developed over decades, these therapies are now standard care but face challenges with patient response and resistance.
- Newer agents targeting pathways like Ang-2/Tie2 have emerged as second-generation treatments.
Purpose of the Study:
- To review the current status of vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) targeted agents.
- To explore the potential of combining first and second-generation anti-angiogenic therapies.
- To discuss strategies for impairing tumor angiogenesis through combined therapeutic approaches.
Main Methods:
- Review of scientific literature on anti-angiogenic therapies.
- Analysis of the roles of VEGF and Ang-2 in tumor angiogenesis.
- Evaluation of preclinical and clinical data on combination therapies targeting the tumor vasculature.
Main Results:
- VEGF targeted agents are established therapies, but patient response and resistance remain significant issues.
- Second-generation agents targeting the Ang-2/Tie2 axis offer new therapeutic avenues.
- Combining first and second-generation agents demonstrates potential for superior outcomes compared to monotherapy.
Conclusions:
- Combination therapy targeting the tumor vasculature, particularly with VEGF and Ang-2 agents, represents a promising strategy.
- Further research is needed to optimize combination regimens and overcome resistance mechanisms.
- Targeting both VEGF and Ang-2 pathways may enhance the efficacy of anti-angiogenic cancer treatment.
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