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Updated: May 4, 2026
Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
Published on: November 23, 2014
Antiangiogenesis beyond VEGF inhibition: a journey from antiangiogenic single-target to broad-spectrum agents
Gabriel Limaverde-Sousa1, Cinthya Sternberg1, Carlos Gil Ferreira1
1Coordination of Clinical Research and Technology Incorporation, National Cancer Institute of Brazil (INCA), Rio de Janeiro, Brazil.
Abstract:
Although the inhibition of angiogenesis is an established modality of cancer treatment, concerns regarding toxicity and drug resistance still constitute barriers to be overcome. For almost a decade since the approval of bevacizumab in 2004, the efforts on antiangiogenic therapeutics have been mainly focused in inhibiting the VEGF pathway. The ongoing understanding of the complexity of the angiogenic process has broadened the spotlight to include concurrent and downstream players to the list of targeted inhibitors. In this review, we summarize the currently existing and the promising antiangiogenic treatments, envisioning an apparent evolutionary trend towards the development of angiogenesis inhibitors of three modalities: single-target, multi-target, and broad-spectrum agents. The clinical efficacy and some structural aspects of monoclonal antibodies, small molecules, endogenous and synthetic angiogenesis inhibitors and their molecular targets are discussed, and the targeting of endothelial cells with the use of cytotoxic drugs in a metronomic schedule is appraised. The reader is invited to revisit current expectations about antiangiogenic therapy in an attempt to set consistent clinical endpoints from which patients could gain real and lasting clinical benefits.
Insights
This review explores antiangiogenic cancer therapies, moving beyond single-target VEGF inhibitors to multi-target and broad-spectrum agents. The goal is to overcome toxicity and resistance for lasting patient benefits.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Antiangiogenic therapy is a key cancer treatment, but toxicity and resistance remain challenges.
- Early efforts focused on vascular endothelial growth factor (VEGF) pathway inhibition.
- Newer research targets the complex angiogenic process with broader strategies.
Purpose of the Study:
- To review current and emerging antiangiogenic treatments.
- To discuss the evolution towards single-target, multi-target, and broad-spectrum agents.
- To re-evaluate clinical endpoints for improved patient outcomes.
Main Methods:
- Literature review of existing and promising antiangiogenic therapies.
- Discussion of monoclonal antibodies, small molecules, and endogenous/synthetic inhibitors.
- Appraisal of metronomic chemotherapy targeting endothelial cells.
Main Results:
- Angiogenesis inhibition is established but faces toxicity and resistance.
- Focus is shifting from single-target (VEGF) to multi-target and broad-spectrum agents.
- Diverse therapeutic modalities including antibodies, small molecules, and metronomic chemotherapy are discussed.
Conclusions:
- Antiangiogenic therapy is evolving towards more comprehensive strategies.
- Development trends indicate a move towards multi-target and broad-spectrum agents.
- Establishing consistent clinical endpoints is crucial for patient benefit.
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