PI3K activation occurs via RAS mutation, loss of PTEN, or by increased expression of growth factor receptors such as ERBB2, EGFR, IGF1R, and VEGFA. On the other hand, the activation of the PI3K/AKT pathway in tumor cells can promote the secretion of VEGFA, both by hypoxia-inducible factor 1 (HIF-1α)-dependent and -independent mechanisms (49). This evidence concerns the gene HIF1A and neoplasm.