The predominant mechanisms by which GPCRs activate PI3K are tissue-specific, and many GPCR ligands, such as sphingosine 1-phosphate, activate PI3Ks.69 GPCRs activate PI3K/Akt signaling by stimulating Ras to thereby activate class I PI3Ks, which regulate cancer and many other diseases. This evidence concerns the gene AKT1 and cancer.