4.7 Review

Anti-Angiogenic Therapy: Current Challenges and Future Perspectives

Journal

Publisher

MDPI
DOI: 10.3390/ijms22073765

Keywords

neo-angiogenesis; anti-angiogenic therapy; cancer therapy; VEGF; new targets; drug resistance

Funding

  1. IPOLFG EPE
  2. iNOVA4Health - Fundacao para a Ciencia e Tecnologia (FCT)/Ministerio da Educacao e Ciencia [UID/Multi/04462/2019]
  3. FCT-MCTES [PD/BD/128337/2017]
  4. Fundação para a Ciência e a Tecnologia [PD/BD/128337/2017, UID/Multi/04462/2019] Funding Source: FCT

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Anti-angiogenic therapy aims to fight cancer by disrupting the nutrient and oxygen supply to tumor cells, mainly by targeting vascular endothelial growth factor (VEGF). While some drugs in this category can enhance immune therapy, they often fall short in terms of efficacy. Researchers believe that targeting alternative angiogenic pathways in combination could be a promising solution.
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.

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