HER2 lacks endogenous ligands, it relies on other EGFR family receptors to form heterodimers for activation, of which HER2/HER3 dimer is the most active and plays a core role in activating MAPK pathway and PI3K/AKT/mTOR pathway in cancer, HER3 overexpression is closely related to HER2, not only that, HER3 steadily plays a role in the progression of CRC [142–144]. Here, PIK3CA is linked to colorectal carcinoma.