Role of HER2
HER2 (ErbB2) is a member of the ErbB family of receptor tyrosine kinases, which also includes epidermal growth factor receptor (EGFR), ErbB3, and HER4.1,2 HER2 is the preferred dimerization partner for ErbB family receptors, despite being the only member that lacks a ligand-binding domain.1-3 Ligand binding and dimerization of these receptors activate signaling pathways that promote cell proliferation and survival.3,4
Mutations in HER2 can lead to overexpression or overactivation, which results in uncontrolled cell proliferation, inhibition of apoptosis, and promotion of tumor growth and spread.2,3,5,6 This was confirmed in preclinical models with documented tumor shrinkage associated with the withdrawal of HER2 expression.2 HER2 insertions are seen across a number of different cancer types, with a high prevalence in non-small cell lung cancer (NSCLC), where more than 50% of HER2 mutations may be exon 20 insertions.7,8
Cocco E, et al. Pharmacol Ther 2019;199:188–196.
Wilding B, et al. Nature Cancer. 2022;3(7):821-36.
Tai W, et al. J Control Release 2010;146(3):264–275.
Hynes NE, et al. Nat Rev Cancer 2005;5(5):341-354.
Gazdar AF. Cancer Metastasis Rev 2010;29(1):37-48.
Connell CM, Doherty GJ. ESMO Open 2017;2(5):e000279.
Mishra R, et al. Oncotarget 2017;8(69):114371–114392.
Vyse S, Huang PH. Signal Transduct Target Ther 2019;4:5.