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Published on: June 30, 2023
Anti-Angiogenic Therapy: Current Challenges and Future Perspectives
Filipa Lopes-Coelho1,2, Filipa Martins1,2, Sofia A Pereira2
1Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal.
Abstract:
Anti-angiogenic therapy is an old method to fight cancer that aims to abolish the nutrient and oxygen supply to the tumor cells through the decrease of the vascular network and the avoidance of new blood vessels formation. Most of the anti-angiogenic agents approved for cancer treatment rely on targeting vascular endothelial growth factor (VEGF) actions, as VEGF signaling is considered the main angiogenesis promotor. In addition to the control of angiogenesis, these drugs can potentiate immune therapy as VEGF also exhibits immunosuppressive functions. Despite the mechanistic rational that strongly supports the benefit of drugs to stop cancer progression, they revealed to be insufficient in most cases. We hypothesize that the rehabilitation of old drugs that interfere with mechanisms of angiogenesis related to tumor microenvironment might represent a promising strategy. In this review, we deepened research on the molecular mechanisms underlying anti-angiogenic strategies and their failure and went further into the alternative mechanisms that impact angiogenesis. We concluded that the combinatory targeting of alternative effectors of angiogenic pathways might be a putative solution for anti-angiogenic therapies.
Insights
Revisiting older anti-angiogenic drugs targeting tumor microenvironment mechanisms may improve cancer treatment. Combining therapies that target alternative pathways shows promise for overcoming current limitations.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Anti-angiogenic therapy aims to starve tumors by inhibiting blood vessel formation.
- Current therapies often target vascular endothelial growth factor (VEGF), a key driver of angiogenesis.
- VEGF also plays a role in immune suppression within the tumor microenvironment.
Purpose of the Study:
- To review molecular mechanisms of anti-angiogenic strategies and their limitations.
- To explore alternative mechanisms impacting angiogenesis.
- To propose novel therapeutic strategies for cancer treatment.
Main Methods:
- Literature review focusing on molecular mechanisms of angiogenesis.
- Analysis of factors contributing to anti-angiogenic therapy failure.
- Investigation of alternative pathways influencing tumor vascularization.
Main Results:
- VEGF-targeted therapies are insufficient in many cancer cases.
- The tumor microenvironment harbors alternative angiogenesis regulators.
- Rehabilitating older drugs targeting these alternative mechanisms is a potential strategy.
Conclusions:
- Combinatorial targeting of alternative angiogenic pathways offers a promising solution.
- Repurposing existing drugs may enhance anti-angiogenic efficacy.
- Future research should focus on multifaceted therapeutic approaches for cancer.
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