ERBB2 and neoplasm: With functional significance, ex20ins lead to constitutive activation of HER2 tyrosine kinase activity and initiate the protumorigenic downstream MEK/ERK/MAPK and PI3K/AKT/mTOR pathway signaling cascade, resulting in increased proliferation and tumor growth (Berns et al., 2007; Spector and Blackwell, 2009; Arcila et al., 2012; Hanker et al., 2013).