CD274 and cancer: Moreover, in the second pathway, the constitutively active mutant Ras activates its immediately downstream factors, including phosphatidylinositol 3-kinase (PI3K), Rac1, and Raf which trigger a sequential activation of multiple downstream factors and eventually induce expressions of many genes such as RhoA/B, EGFR, VEGF, and PD-L1 in cancer cells [2,6,15,16,17].