HER4, which can be activated by ligands like heparin-binding EGF-like growth factor, neuregulins, and betacellulin, has been implicated in promoting cell proliferation and metastasis while inhibiting differentiation through PI3K/Akt and Shc pathway activation.57 The inhibition of HER3 or the absence of HER4 leads to increased apoptosis in CRC cells, potentially through a HER3–HER4 heterodimer-dependent Akt pathway. Here, PIK3CA is linked to colorectal carcinoma.