Furthermore, in these models, Bv8 inhibition and anti-VEGF-A agents have a cumulative effect, demonstrating that both Bv8 and VEGF-A contribute to tumor neoangiogenesis.34 Considering TAN negative impact on bevacizumab efficacy, TAN infiltration should be specifically analyzed in clinical trials that combine ICIs and antibodies against VEGFR-2 (tanibirumab and ramucirumab), or VEGFR-2 inhibitors, such as apatinib. The gene discussed is PROK2; the disease is neoplasm.