Antiangiogenic therapy: how far is it to upgrade?

Abstract

Early vascular-targeted drugs represented by VEGF single-pathway inhibitors pioneered the idea of regulating the tumor growth microenvironment and enhanced the chemotherapy effect in a variety of tumors. However, their shortcomings of “only winning PFS but not OS” have gradually revealed and warned that drug-resistant growth of tumors is unavoidable after long-term use. The activation of intracellular bypass signaling after inhibiting a single target may be an important reason. In order to eliminate this problem, attempts have been made to expand the combination of drug types and increase the intensity of drug treatment. The possibility of replacing single-target anti-angiogenic therapeutic drugs with multiple targets has also be explored. A new generation of “dual-dimension, multi-pathway” drugs that simultaneously inhibit multiple targets both in tumors and microvascular endothelial cells can be used either as single drugs in multiple tumor types, or in combination with chemotherapy, EGFR-TKI, or even immunological drugs. It demonstrates good efficacy and great potential and hope for upgrading vascular targeted therapy. It also enlightens us that future treatment and new drug development strategies cannot rely solely on the most precise target inhibition, but should have a “dual-dimension, multi-pathway” integration concept that looks at the overall situation from one corner.