Inhibition of PI3K has been shown to block activation of mitogen-activated kinase (MAPK) independent of EGFR in A431 cells (Graness et al., 2000), suggesting a prominent role for therapies targeting PI3K in vulvar cancer and as mentioned previously signaling through PGE2 receptor EP4 can lead to activation of PI3K. Here, PTGER4 is linked to vulva cancer.