Anti-Angiogenic Therapy: Current Challenges and Future Perspectives

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.

Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex

“…Cystine avoids ferroptosis and increases glutathione availability, which avoids the angiogenic switch and promotes vessel stabilization. Both processes are pivotal for the prevention of vascular remodeling [ 79 ].…”

Personalized functional profiling using ex-vivo patient-derived spheroids points out the potential of an antiangiogenic treatment in a patient with a metastatic lung atypical carcinoid

“… 14 The release of pro-angiogenic factors by cancer cells and tumor microenvironment stimulates the migration and proliferation of endothelial cells and triggers vessel formation. 15 Apart from angiogenesis, other mechanisms account for tumor vascularization, in particular vessel co-option, a process whereby tumor cells incorporate and use preexisting vessels from the surrounding normal tissue to proliferate and spread, and vascular mimicry which is the acquisition by tumor cells of an endothelial-like phenotype leading to vascular-like structures. 15 , 16 …”

Investigation of Lupeol as Anti-Melanoma Agent: An In Vitro-In Ovo Perspective

“…Angiogenesis is a process of real importance in oncogenesis, given that malignant cells need oxygen and nutrients to grow, which are transported through blood vessels. Anti-angiogenic compounds have been developed to inhibit the formation of new blood vessels and also to block tumor growth [ 40 , 41 , 42 ]. Lupeol raises interest in terms of antiangiogenic effect, noting in the present study that after 24 h of treatment, LUP caused a considerable decrease in neovascularization, and at the chorioallantoic membrane level can be seen areas without vascularization ( Figure 7 ).…”