ERBB3 V104M

COS7 cells transiently transfected with the HER3-V104L mutation in the presence of HER binding partners showed higher expression of p-HER3, p-ERK1/2 versus HER3-WT in a NRG-independent manner without any change in AKT signaling. Overall, this study shows the clinical relevance of the HER3 V104L and the V104M mutations and its response to HER2, PI3K and ERK inhibitors.

Molecular profiling of liquid biopsies at baseline identified alterations that could impact on patient outcomes. Our data suggest that the presence of BRAF pathogenic variants may be a good prognostic factor in stage IV NSCLC patients treated with immunotherapy or chemo-immunotherapy, while pathogenic mutations in ERBB3 could be a biomarker of high risk of disease progression. Additional studies analyzing larger cohorts of patients are needed to clarify these hypotheses.