Fig. 2
From: Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment
a Main angiogenesis pathways and anti-angiogenesis agents. VEGF-VEGFR2 promotes the proliferation and migration of endothelial cell primarily by activating downstream PLCγ-PKC-Raf-MAPK and Grb2-Gab1-MAPK/PI3K-Akt signaling pathways. In addition, VEGF-VEGFR2 could increase vascular permeability by activating VEGFR2–TSAd–Src-cadherin and PI3K–Akt–eNOS–NO signaling pathways. Anti-angiogenesis agents consist of three types: (I) anti-VEGF monoclonal antibody (mAb) such as bevacizumab and decoy VEGF-trap receptor such as aflibercept; (II) anti-VEGFR2 mAb (ramucirumab); (III) VEGFR tyrosine kinase inhibitor (TKI). b Normalization window of anti-angiogenesis treatment. When pro-angiogenic (pro) factors balance with anti-angiogenic (anti) factors, abnormal tumor vessels transform into normal-like phenotype (green). Vessel normalization is a transient status changing along with the time and dose of treatment