The HER2 pathway promotes cell growth and division when it is functioning normally; however, when it is overexpressed, cell growth accelerates beyond its normal limits. In some types of cancer, the pathway is exploited to promote rapid cell growth and proliferation and hence tumor formation. The EGF pathway includes the receptors HER1 (EGFR), HER2, HER3, and HER4; the binding of ligands (e.g. EGF etc.) to HER receptors is required to activate the pathway. The pathway initiates the MAP kinase pathway as well as the PI3 kinase/AKT pathway, which in turn activates the NF-κB pathway. In cancer cells the HER2 protein can be expressed up to 100 times more than in normal cells (2 million versus 20,000 per cell). This overexpression leads to strong and constant proliferative signaling and hence tumor formation. Overexpression of HER2 also causes deactivation of checkpoints, allowing for even greater increases in proliferation.
