Progress in Treatment of Non-Small Cell Lung Cancer Harboring HER2 Aberrations

Epidermal growth factor receptor 2 (HER2/ErbB2/neu), a member of ErbB receptor tyrosine kinase family, forms homo- or heterodimers with ErbB1 (HER1/EGFR), ErbB3 (HER3), or ErbB4 (HER4), to activate signal transduction pathways and promote proliferation, differentiation and tumorigenesis. Preliminary clinical trials of monoclonal antibodies, antibody conjugates and small-molecule tyrosine kinase inhibitors targeting HER2 have indicated that HER2 is a potential therapeutic target in non-small cell lung cancer (NSCLC). HER2 aberrations in NSCLC patients mainly include mutation, amplification, and overexpression. While there are significant differences in the outcome of NSCLC with these HER2 changes, no consensus has been reached for the incidence, detection method and targeted treatments for the three types of HER2 aberration. HER2 mutation is generally considered to have more clinical relevance and response to HER2-targeted therapies. In this review, we discuss HER2 alterations in NSCLC, including diagnostic challenges and treatment strategies particular to the HER2 mutation.