PTEN and neoplasm: The HER2 receptor, like most receptor tyrosine kinases, influences three major intracellular signaling pathways, all involved in tumor survival and proliferation: the PI3K-AKT pathway (activated by HER2 dimerization at the cell surface and impacted by mutations in the PIK3CA, AKT1, and PTEN genes), the MAP-kinase (MAPK) pathway (a kinase cascade with signal amplification at each new phosphorylation step and impacted by KRAS, NRAS, and BRAF mutations), and the JAK-STAT pathway (an independent pathway not affected by mutations in genes affecting the other two pathways).