Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions

By N. Vasudev, Andrew R Reynolds. Angiogenesis, 2014

684 citations recorded by the source corpus.

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies.

Subfields: Molecular Biology, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/e3c97feaa816316233c77a624277c37f9fdb6524

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In Pulmonary and Respiratory Medicine

Citations in the corpus

Angiogenic signaling pathways and anti-angiogenic therapy for cancer (2023, background): “Despite considerable efforts, there are few biomarkers responding to angiogenesis approved for clinical application.(172,519,520) Given the variable results from anti-angiogenic Table 3.”
ANTIANGIOGENESIS STRATEGIES REVISITED: FROM STARVING TUMORS TO ALLEVIATING HYPOXIA (2014, positive): “…include Ang2/Tie2/VE-PTP and HGF/ cMET, which play important roles in vascular structure and function (e.g., pericyte coverage and permeability) and cell invasion (Figure 3) (Sennino et al., 2012; Vasudev and Reynolds, 2014; M. Hidalgo et al., 2014, ASCO Annual Meeting Proceedings, abstract).”
Combined antiangiogenic and anti–PD-L1 therapy stimulates tumor immunity through HEV formation (2017, background): “Notwithstanding the favorable effects of these inhibitors in some patients, they improve progression-free survival and quality of life, but are unfortunately short-lived and modestly influence overall survival in most patients (12, 15, 16).”